Morbidity and Mortality Weekly Report
Recommendations and Reports
December 8, 2006 / Vol. 55 / No. RR-16
A Comprehensive Immunization Strategy
to Eliminate Transmission of Hepatitis B
Virus Infection in the United States
Recommendations of the Advisory
Committee on Immunization Practices (ACIP)
Part II: Immunization of Adults
INSIDE: Continuing Education Examination
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Centers for Disease Control and Prevention
Prevention
MMWR
CONTENTS
The MMWR series of publications is published by the Coordinating
Center for Health Information and Service, Centers for Disease
Control and Prevention (CDC), U.S. Department of Health and
Human Services, Atlanta, GA 30333.
Suggested Citation: Centers for Disease Control and Prevention.
[Title]. MMWR 2006;55(No. RR-#):[inclusive page numbers].
Centers for Disease Control and Prevention
Julie L. Gerberding, MD, MPH
Director
Tanja Popovic, MD, PhD
(Acting) Chief Science Officer
James W. Stephens, PhD
(Acting) Associate Director for Science
Steven L. Solomon, MD
Director, Coordinating Center for Health Information and Service
Jay M. Bernhardt, PhD, MPH
Director, National Center for Health Marketing
Judith R. Aguilar
(Acting) Director, Division of Health Information Dissemination (Proposed)
Editorial and Production Staff
Frederic E. Shaw, MD, JD
(Acting) Editor, MMWR Series
Suzanne M. Hewitt, MPA
Managing Editor, MMWR Series
Teresa F. Rutledge
Lead Technical Writer-Editor
Jeffrey D. Sokolow, MA
Project Editor
Beverly J. Holland
Lead Visual Information Specialist
Lynda G. Cupell
Malbea A. LaPete
Visual Information Specialists
Quang M. Doan, MBA
Erica R. Shaver
Information Technology Specialists
Editorial Board
William L. Roper, MD, MPH, Chapel Hill, NC, Chairman
Virginia A. Caine, MD, Indianapolis, IN
David W. Fleming, MD, Seattle, WA
William E. Halperin, MD, DrPH, MPH, Newark, NJ
Margaret A. Hamburg, MD, Washington, DC
King K. Holmes, MD, PhD, Seattle, WA
Deborah Holtzman, PhD, Atlanta, GA
John K. Iglehart, Bethesda, MD
Dennis G. Maki, MD, Madison, WI
Sue Mallonee, MPH, Oklahoma City, OK
Stanley A. Plotkin, MD, Doylestown, PA
Patricia Quinlisk, MD, MPH, Des Moines, IA
Patrick L. Remington, MD, MPH, Madison, WI
Barbara K. Rimer, DrPH, Chapel Hill, NC
John V. Rullan, MD, MPH, San Juan, PR
Anne Schuchat, MD, Atlanta, GA
Dixie E. Snider, MD, MPH, Atlanta, GA
John W. Ward, MD, Atlanta, GA
Introduction ......................................................................... 2
Methods .............................................................................. 3
Major Updates to the Recommendations ............................. 3
Background ......................................................................... 3
Clinical Features and Natural History of HBV Infection ..... 3
Interpretation of Serologic Markers of HBV Infection ......... 4
Epidemiology of HBV Infection .......................................... 5
Prophylaxis Against HBV Infection ....................................... 8
Hepatitis B Vaccine ........................................................... 8
Hepatitis B Immune Globulin ............................................ 9
Adult Vaccination Schedules and Results of Vaccination ..... 10
Preexposure Vaccination ................................................. 10
Postexposure Prophylaxis ................................................ 12
Vaccine Safety ................................................................... 12
Vaccine Reactogenicity .................................................... 12
Adverse Events ............................................................... 12
Contraindications and Precautions .................................. 13
Implementation Barriers and Rationale
for New Recommendations .............................................. 13
Recommendations and Implementation Strategies
for Hepatitis B Vaccination of Adults ................................ 15
Recommendations .......................................................... 15
Implementation Strategies .............................................. 16
Acknowledgments ............................................................. 18
References ......................................................................... 18
Appendices ....................................................................... 26
Continuing Education Activity ......................................... CE-1
Disclosure of Relationship
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have no financial interests or other relationships with the
manufacturers of commercial products, suppliers of commercial
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Vol. 55 / RR-16
Recommendations and Reports
A Comprehensive Immunization Strategy
to Eliminate Transmission of Hepatitis B Virus Infection
in the United States
Recommendations of the Advisory Committee on Immunization
Practices (ACIP) Part II: Immunization of Adults
Prepared by
Eric E. Mast, MD1
Cindy M. Weinbaum, MD1
Anthony E. Fiore, MD1
Miriam J. Alter, PhD1
Beth P. Bell, MD1
Lyn Finelli, DrPH1
Lance E. Rodewald, MD2
John M. Douglas, Jr., MD3
Robert S. Janssen, MD4
John W. Ward, MD1
1
Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (proposed)
2
Immunization Services Division, National Center for Immunization and Respiratory Diseases (proposed)
3
Division of STD Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (proposed)
4
Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (proposed)
Summary
Hepatitis B vaccination is the most effective measure to prevent hepatitis B virus (HBV) infection and its consequences,
including cirrhosis of the liver, liver cancer, liver failure, and death. In adults, ongoing HBV transmission occurs primarily among
unvaccinated persons with behavioral risks for HBV transmission (e.g., heterosexuals with multiple sex partners, injection-drug
users [IDUs], and men who have sex with men [MSM]) and among household contacts and sex partners of persons with chronic
HBV infection.
This report, the second of a two-part statement from the Advisory Committee on Immunization Practices (ACIP), provides
updated recommendations to increase hepatitis B vaccination of adults at risk for HBV infection. The first part of the ACIP
statement, which provided recommendations for immunization of infants, children, and adolescents, was published previously
(CDC. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States:
recommendations of the Advisory Committee on Immunization Practices [ACIP]. Part 1: immunization of infants, children,
and adolescents. MMWR 2005;54[No. RR-16]:1–33).
In settings in which a high proportion of adults have risks for HBV infection (e.g., sexually transmitted disease/human immu­
nodeficiency virus testing and treatment facilities, drug-abuse treatment and prevention settings, health-care settings targeting
services to IDUs, health-care settings targeting services to MSM, and correctional facilities), ACIP recommends universal hepati­
tis B vaccination for all unvaccinated adults. In other primary care and specialty medical settings in which adults at risk for HBV
infection receive care, health-care providers should inform all
patients about the health benefits of vaccination, including
The material in this report originated in the National Center for HIV/
risks for HBV infection and persons for whom vaccination is
AIDS, Viral Hepatitis, STD, and TB Prevention (proposed), Kevin
recommended, and vaccinate adults who report risks for HBV
A. Fenton, MD, PhD, Director; the Division of Viral Hepatitis, John
infection and any adults requesting protection from HBV
W. Ward, MD, Director; the Division of STD Prevention, John M.
Douglas, Jr., MD, Director; and the Division of HIV/AIDS
infection. To promote vaccination in all settings, health-care
Prevention, Robert S. Janssen, MD, Director; the National Center
providers should implement standing orders to identify adults
for Immunization and Respiratory Diseases, Anne Schuchat, MD,
recommended for hepatitis B vaccination and administer vac­
Director; and the Immunization Services Division, Lance E. Rodewald,
MD, Director.
cination as part of routine clinical services, not require
Corresponding preparer: Eric E. Mast, MD, Division of Viral
acknowledgment of an HBV infection risk factor for adults to
Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and
receive vaccine, and use available reimbursement mechanisms
TB Prevention (proposed), 1600 Clifton Road, NE, MS G-37, Atlanta,
GA 30333. Telephone: 404-718-8500; Fax: 404-718-8595; E-mail:
to remove financial barriers to hepatitis B vaccination.
[email protected].
1
2
MMWR
Introduction
Hepatitis B is a disease caused by the hepatitis B virus (HBV),
which is transmitted through percutaneous (i.e., puncture
through the skin) or mucosal (i.e., direct contact with
mucous membranes) exposure to infectious blood or body flu­
ids. HBV can cause chronic infection, resulting in cirrhosis of
the liver, liver cancer, liver failure, and death. Persons with
chronic infection also serve as the main reservoir for continued
HBV transmission. Although chronic infection is more likely
to develop in persons infected as infants or young children,
rates of new infection and acute disease are highest among adults.
Hepatitis B vaccination is the most effective measure to pre­
vent HBV infection and its consequences. Since recommen­
dations for hepatitis B vaccination were first issued in 1982, a
comprehensive strategy to eliminate HBV transmission in the
United States has evolved (1–5). This strategy includes
1) universal vaccination of infants beginning at birth, 2) pre­
vention of perinatal HBV infection through routine screening
of all pregnant women for hepatitis B surface antigen (HBsAg)
and postexposure immunoprophylaxis of infants born to
HBsAg-positive women or to women with unknown HBsAg
status, 3) vaccination of all children and adolescents who were
not vaccinated previously, and 4) vaccination of previously
unvaccinated adults at risk for HBV infection (Box 1).
To date, immunization strategies for infants, children, and
adolescents have been implemented with considerable suc­
cess. Recent estimates indicate that approximately 95% of
pregnant women are tested for HBsAg and that case manage­
ment has been effective in ensuring high levels of initiation
and completion of postexposure immunoprophylaxis among
infants born to HBsAg-positive women (6). Hepatitis B vac­
cine has been integrated successfully into the childhood vac­
cination schedule, and infant vaccination coverage levels now
are equivalent to those of other vaccines in the childhood
BOX 1. Immunization strategy to eliminate transmission of
hepatitis B virus (HBV) in the United States
• Universal vaccination of infants beginning at birth
• Prevention of perinatal HBV infection through
— routine screening of all pregnant women for
hepatitis B surface antigen (HBsAg), and
— immunoprophylaxis of infants born to HBsAg­
positive women or to women with unknown HBsAg
status
• Routine vaccination of previously unvaccinated children
and adolescents
• Vaccination of previously unvaccinated adults at risk
for HBV infection
December 8, 2006
schedule (7). Vaccination coverage among adolescents also has
increased substantially; preliminary data from 2003 indicated
that approximately 50%–60% of adolescents aged 13–15 years
have records indicating vaccination (with 3 doses) against hepa­
titis B (8). During 1990–2005, incidence of acute hepatitis B
in the United States declined 78%. The greatest decline (96%)
occurred among children and adolescents, coincident with an
increase in hepatitis B vaccination coverage. This success can
be attributed in part to the established infrastructure for vac­
cine delivery to children and to federal support for perinatal
hepatitis B prevention programs.
Among adults, ongoing HBV transmission occurs prima­
rily among unvaccinated adults with risk behaviors for HBV
transmission (e.g., heterosexuals with multiple sex partners,
injection-drug users [IDUs], and men who have sex with men
[MSM]) and among household contacts and sex partners of
persons with chronic HBV infection. During 2000–2004, selfreported hepatitis B vaccination coverage among adults at risk
for HBV infection increased from 30% to 45% (9); this
increase in vaccination coverage likely contributed to the 35%
decline in acute hepatitis B incidence that occurred during
this period (from 3.7 to 2.4 per 100,000 population). How­
ever, incidence of acute hepatitis B remains highest among
adults, who accounted for approximately 95% of an estimated
51,000 new HBV infections in 2005. Although acceptance of
vaccination is high among adults offered vaccination (10),
the low adult vaccination coverage reflects the lack of hepati­
tis B vaccination services in settings in which a high propor­
tion of adults have risk factors for HBV infection (e.g., sexually
transmitted disease [STD]/human immunodeficiency virus
[HIV] testing and treatment facilities, drug-abuse treatment
and prevention settings, health-care settings targeting services
to IDUs, health-care settings targeting services to MSM, and
correctional facilities) and missed opportunities to vaccinate
adults at risk for HBV infection in primary care and specialty
medical settings. Although hepatitis B incidence among adults
is expected to continue to decline during the next decade as
successive cohorts of persons vaccinated in infancy, childhood,
and adolescence reach adulthood, new implementation strat­
egies are needed to protect unvaccinated adults at risk for HBV
infection.
This report provides updated guidance from the Advisory
Committee on Immunization Practices (ACIP) to increase hepa­
titis B vaccination coverage among adults. It includes recom­
mendations regarding which adults should receive hepatitis B
vaccine and outlines implementation strategies to ensure that
those adults are vaccinated. The first part of this statement,
which provided recommendations for immunization of infants,
children, and adolescents, was published previously (11).
Vol. 55 / RR-16
Recommendations and Reports
Methods
In response to continuing low rates of hepatitis B vaccina­
tion among adults at risk for HBV infection, ACIP’s Hepati­
tis Vaccines Work Group met multiple times during October
2004–September 2005 to review previous guidelines and make
recommendations for improving vaccination coverage in
adults. The work group examined the progress made since
1991 in implementing the U.S. strategy to eliminate HBV
transmission (e.g., vaccination coverage data and hepatitis B
disease rates), surveillance data on missed opportunities for
hepatitis B vaccination among adults with acute hepatitis B,
and results of cost-effectiveness analyses. In addition, demon­
stration projects conducted in settings in which a high pro­
portion of clients were at risk for HBV infection identified
the components of successful adult hepatitis B vaccination
programs and ongoing challenges to implementing adult hepa­
titis B vaccination.
In January 2005, the proposed recommendations were
posted online for public comment. In May 2005, CDC con­
vened a meeting of external consultants, including research­
ers, physicians, state and local public health professionals,
immunization program directors, and directors of viral hepa­
titis, STD, and HIV/AIDS prevention programs, to obtain
input into the draft recommendations and consider the feasi­
bility of the recommended strategies. In October 2005, the
revised recommendations were approved by ACIP.
Major Updates
to the Recommendations
This report updates ACIP recommendations published pre­
viously for hepatitis B vaccination of adults (3). The primary
changes from previous recommendations are as follows:
• In settings in which a high proportion of persons are likely
to be at risk for HBV infection (e.g., STD/HIV testing
and treatment facilities, drug-abuse treatment and pre­
vention settings, health-care settings targeting services to
IDUs, health-care settings targeting services to MSM, and
correctional facilities), ACIP recommends universal hepa­
titis B vaccination for all adults who have not completed
the vaccine series.
• In primary care and specialty medical settings, ACIP rec­
ommends implementation of standing orders to identify
adults recommended for hepatitis B vaccination and
administer vaccination as part of routine services. To
ensure vaccination of adults at risk for HBV infection
who have not completed the vaccine series, ACIP recom­
mends the following implementation strategies:
3
— Provide information to all adults regarding the health
benefits of hepatitis B vaccination, including risk fac­
tors for HBV infection and persons for whom vacci­
nation is recommended.
— Help all adults assess their need for vaccination by
obtaining a history that emphasizes risks for sexual
transmission and percutaneous or mucosal exposure
to blood.
— Vaccinate all adults who report risks for HBV infection.
— Vaccinate all adults requesting protection from HBV
infection, without requiring them to acknowledge a
specific risk factor.
Background
Clinical Features and Natural History
of HBV Infection
HBV is a 42-nm DNA virus classified in the Hepadnaviridae
family. The liver is the primary site of HBV replication. After
a susceptible person is exposed, the virus enters the liver via
the bloodstream; no evidence exists indicating that the virus
replicates at mucosal surfaces. HBV infection can produce
either asymptomatic or symptomatic infection. The average
incubation period is 90 days (range: 60–150 days) from
exposure to onset of jaundice and 60 days (range: 40–90 days)
from exposure to onset of abnormal serum alanine aminotrans­
ferase (ALT) levels (12,13).
The onset of acute disease typically is insidious. Infants,
children aged <5 years, and immunosuppressed adults with
newly acquired HBV infection typically are asymptomatic,
whereas 30%–50% of children aged >5 years and adults have
initial clinical signs or symptoms (14). When present, clinical
symptoms and signs can include anorexia, malaise, nausea,
vomiting, abdominal pain, and jaundice. Extrahepatic mani­
festations of disease (e.g., skin rashes, arthralgias, and arthri­
tis) also can occur (15). The fatality rate among persons with
reported cases of acute hepatitis B is 0.5%–1.0%, with the
highest rates in adults aged >60 years; however, because a sub­
stantial number of infections are asymptomatic and therefore
are not reported, the overall fatality rate among all persons
with HBV infection likely is lower (16).
Approximately 95% of primary infections in adults with nor­
mal immune status are self-limited, with elimination of virus
from blood and subsequent lasting immunity to reinfection.
Chronic infection occurs in <5% of infected persons aged >5
years, approximately 30% of infected children aged <5 years,
and approximately 90% of infected infants, with continuing
viral replication in the liver and persistent viremia (14,17–19).
4
MMWR
Primary infections become chronic more frequently in immu­
nosuppressed persons (e.g., hemodialysis patients and persons
with HIV infection) (19,20) and persons with diabetes (21).
Overall, approximately 25% of persons who become chroni­
cally infected during childhood and 15% of those who become
chronically infected after childhood die prematurely from cir­
rhosis or liver cancer; the majority remain asymptomatic until
onset of cirrhosis or end-stage liver disease (22).
No specific treatment exists for acute hepatitis B; supportive
care is the mainstay of therapy. Persons who have chronic HBV
infection require medical evaluation and regular monitoring
(23–25). Therapeutic agents approved by the Food and Drug
Administration (FDA) for treatment of chronic hepatitis B can
achieve sustained suppression of HBV replication and remis­
sion of liver disease in certain persons (24). Periodic screening
with ultrasonography and alfa-fetoprotein has been demon­
strated to enhance early detection of hepatocellular carcinoma
(HCC) (25). Certain chronically infected persons with HCC
have experienced long-term survival after resection of small
hepatocellular carcinomas, and persons who were screened had
HCC detected at an earlier stage and had a substantial survival
advantage compared with historical controls (25); however, data
from controlled studies are lacking. Guidance for the diagnosis
and management of hepatitis B is available (26).
December 8, 2006
Interpretation of Serologic Markers
of HBV Infection
Antigens and antibodies associated with HBV infection in­
clude HBsAg and antibody to HBsAg (anti-HBs), hepatitis B
core antigen (HBcAg) and antibody to HBcAg (anti-HBc),
and hepatitis B e antigen (HBeAg) and antibody to HBeAg
(anti-HBe). At least one serologic marker is present during
each of the different phases of HBV infection (13,27). The
serologic markers typically used to differentiate between acute,
resolving, and chronic infection are HBsAg, anti-HBc, and
anti-HBs (Table 1). HBeAg and anti-HBe screening typically
is used for the management of patients with chronic infec­
tion. Serologic assays are available commercially for all mark­
ers except HBcAg because no free HBcAg circulates in blood.
The presence of a confirmed HBsAg-positive result in
serum indicates active HBV infection. All HBsAg-positive per­
sons should be considered infectious. In newly infected per­
sons, HBsAg is the only serologic marker detected during the
first 3–5 weeks after infection. The average time from expo­
sure to detection of HBsAg is 30 days (range: 6–60 days)
(12,13). Highly sensitive single-sample nucleic acid tests can
detect HBV DNA in the serum of an infected person 10–20
days before detection of HBsAg (28). Transient HBsAg posi­
tivity has been reported for up to 18 days after hepatitis B
vaccination and is clinically insignificant (29,30).
TABLE 1. Typical interpretation of serologic test results for hepatitis B virus infection
Serologic marker
Total
anti-HBc†
IgM§
anti-HBc
Anti-HBs¶
–**
–
–
–
Never infected
+††§§
–
–
–
Early acute infection; transient (up to 18 days) after vaccination
+
+
+
–
Acute infection
–
+
+
+ or –
–
+
–
+
Recovered from past infection and immune
+
+
–
–
Chronic infection
–
+
–
–
False-positive (i.e., susceptible); past infection; “low-level”
chronic infection;¶¶ or passive transfer of anti-HBc to infant
born to HBsAg-positive mother
–
–
–
+
Immune if concentration is >10 mIU/mL after vaccine series
completion;*** passive transfer after hepatitis B immune
globulin administration
HBsAg*
Interpretation
Acute resolving infection
* Hepatitis B surface antigen.
Antibody to hepatitis B core antigen.
Immunoglobulin M.
Antibody to HBsAg.
** Negative test result.
†† Positive test result.
§§ To ensure that an HBsAg-positive test result is not a false-positive, samples with reactive HBsAg results should be tested with a licensed neutralizing
confirmatory test if recommended in the manufacturer’s package insert.
¶¶ Persons positive only for anti-HBc are unlikely to be infectious except under unusual circumstances in which they are the source for direct percutane­
ous exposure of susceptible recipients to large quantities of virus (e.g., blood transfusion or organ transplant).
*** Milli-international units per milliliter.
†
§
¶
Vol. 55 / RR-16
Recommendations and Reports
Anti-HBc appears at the onset of symptoms or liver-test
abnormalities in acute HBV infection and persists for life.
Acute or recently acquired infection can be distinguished by
the presence of the immunoglobulin M (IgM) class of antiHBc, which is detected at the onset of acute hepatitis B and
persists for up to 6 months if the disease resolves. In patients
who have chronic HBV infection, IgM anti-HBc can persist
during viral replication at low levels that typically are not
detectable by assays used in the United States. However, per­
sons with exacerbations of chronic infection can test positive
for IgM anti-HBc (31). Using IgM anti-HBc testing for diag­
nosis of acute hepatitis B should be limited to persons for
whom clinical evidence of acute hepatitis or an epidemiologic
link to a case has been identified because the positive predic­
tive value of this test is low in asymptomatic persons.
In persons who recover from HBV infection, HBsAg is elimi­
nated from the blood, and anti-HBs develops, typically within
3–4 months. The presence of anti-HBs typically indicates
immunity from HBV infection. Infection or immunization with
one serotype of HBV confers immunity to all serotypes. In
addition, anti-HBs can be detected for several months after hepa­
titis B immune globulin (HBIG) administration. Persons who
recover from natural infection typically will be positive for both
anti-HBs and anti-HBc, whereas persons who respond to hepa­
titis B vaccine have only anti-HBs. In persons who become
chronically infected, HBsAg and anti-HBc persist, typically for
life. HBsAg will become undetectable in approximately 0.5%–
2% of persons with chronic infection yearly; anti-HBs will
occur in the majority of these persons (32–35).
In certain persons, the only HBV serologic marker detected
in serum is anti-HBc. Isolated anti-HBc can be detected after
HBV infection in persons who have recovered but whose antiHBs levels have waned. Certain chronically infected persons
with anti-HBc alone have circulating HBsAg not detectable
by commercial serology. HBV DNA has been detected in the
blood of <10% of persons with isolated anti-HBc (36,37).
These persons are unlikely to be infectious except under cir­
cumstances in which they are a source for direct percutaneous
exposure of susceptible recipients to substantial quantities of
virus (e.g., through blood transfusion or organ transplanta­
tion) (38). An isolated anti-HBc result also can be a falsepositive. Typically, the frequency of isolated anti-HBc relates
directly to the prevalence of HBV infection in the popula­
tion. In populations with a high prevalence of HBV infec­
tion, isolated anti-HBc likely indicates previous infection, with
loss of anti-HBs. For persons in populations with a low preva­
lence of HBV infection, isolated anti-HBc is found in
approximately 10%–20% of persons with serologic markers
of HBV infection (37) and often represents a false-positive
reaction; the majority of these persons have a primary anti-
5
HBs response after a 3-dose series of hepatitis B vaccine
(39,40).
HBeAg can be detected in the serum of persons with acute
or chronic HBV infection. The presence of HBeAg correlates
with high levels of viral replication (i.e., HBV DNA levels
typically of 107–109 IU/mL, indicating high infectivity)
(41,42). Loss of HBeAg correlates with low levels (i.e., HBV
DNA levels of <105 IU/mL) of replicating virus, although
certain HBeAg-negative persons have HBV DNA levels up to
108–109 IU/mL (43). A mutation in the precore region of
the HBV genome has been identified in HBeAg-negative per­
sons with high HBV DNA levels (44,45).
Epidemiology of HBV Infection
HBV is transmitted by percutaneous or mucosal exposure
to infectious blood or body fluids. Although HBsAg has been
detected in multiple body fluids, only serum, semen, and
saliva have been demonstrated to be infectious (46,47). HBV
is concentrated most highly in serum, with lower concentra­
tions in semen and saliva. All HBsAg-positive persons are
infectious, but those who are also HBeAg positive are more
infectious because their blood contains high titers of HBV
(typically HBV DNA levels of 107–109 IU/mL) (41,42). HBV
is comparatively stable in the environment and remains viable
for >7 days on environmental surfaces at room temperature
(48). HBV DNA at concentrations of 102–103 IU/mL can
be present on environmental surfaces in the absence of any
visible blood and still cause transmission (48,49).
For adults, the two primary sources of HBV infection are
sexual contact and percutaneous exposure to blood. Personto-person transmission of HBV also can occur in settings
involving nonsexual interpersonal contact over an extended
period (e.g., among household contacts of a person with
chronic HBV infection and developmentally disabled persons
living in a long-term–care facility).
HBV is transmitted efficiently by sexual contact among
heterosexuals and among MSM. Risk factors associated with
sexual transmission among heterosexuals include having
unprotected sex with an infected partner, having unprotected
sex with more than one partner, and history of another STD.
Risk factors associated with sexual transmission among MSM
include having multiple sex partners, history of another STD,
and anal intercourse.
Percutaneous transmission of HBV can occur from receipt
of blood transfusion or organ or tissue transplant from an
infectious donor; injection-drug use, including sharing of
injection-preparation equipment; and frequent exposure to
blood or needles among health-care workers. In the United
States, donor selection procedures and routine testing of
MMWR
donors have made transmission of HBV via transfusion of
whole blood and blood components a rare occurrence (50,51).
Persons with hemophilia who received plasma-derived clot­
ting factor concentrates were previously at high risk for HBV
infection, but such transmission has been eliminated through
viral inactivation procedures and use of recombinant clotting
factor concentrates. Among persons with bleeding disorders
treated at U.S. hemophilia treatment centers during 1998–
2002, no infections with viral hepatitis, including HBV, were
attributable to blood products received during that time (52).
Outbreaks of HBV infection from exposure to contaminated
equipment used for therapeutic injections and other health­
care–related procedures, tattooing, and acupuncture also have
been reported, although such exposures among patients with
acute hepatitis B are reported rarely (53–57). In the majority
of cases, transmission resulted from noncompliance with
aseptic techniques for administering injections and recom­
mended infection-control practices designed to prevent
cross-contamination of medical equipment and devices. No
infections have been demonstrated in susceptible persons who
had oral mucous membrane exposure to HBsAg-positive saliva,
but transmission has occurred through a human bite and has
been demonstrated in animals by subcutaneous inoculation
of saliva (46,58–60).
Persons living with chronically infected persons are at risk
for HBV infection through percutaneous or mucosal expo­
sures to blood or infectious body fluids (e.g., sharing a tooth­
brush or razor, contact with exudates from dermatologic
lesions, or contact with HBsAg-contaminated surfaces). Per­
sons with chronic HBV infection also can transmit HBV in
other settings (e.g., schools, child care centers, or facilities for
developmentally disabled persons), especially if they behave
aggressively or have medical problems (e.g., exudative derma­
titis or open skin lesions) that increase the risk for exposure to
blood or serous secretions.
Adults at Risk for HBV Infection
In the United States in 2005, the highest incidence of acute
hepatitis B was among adults aged 25–45 years (Figure 1).
Approximately 79% of newly acquired cases of hepatitis B are
associated with high-risk sexual activity or injection-drug use;
other known exposures (i.e., occupational, household, travel,
and health-care–related) together account for 5% of new cases,
and 16% deny a specific risk factor for infection (61; CDC,
unpublished data, 2001–2005).
Adults at risk for infection by sexual exposure. The most
common source of HBV infection among adults in the United
States is sexual contact. Heterosexual transmission accounts
for approximately 39% of new HBV infections among adults,
December 8, 2006
FIGURE 1. Reported incidence* of acute hepatitis B, by age
group and sex — United States, 2005
<5
Female
5–9
Male
10–14
15–19
Age group (yrs)
6
20–24
25–29
30–34
35–39
40–44
45–49
50–54
55–59
>60
4.0
3.0
2.0
1.0
0
1.0
2.0
3.0
4.0
Incidence
* Per 100,000 population.
and transmission among MSM accounts for approximately
24% (CDC, unpublishe data, 2001–2005). Serologic evidence
of HBV infection (i.e., anti-HBc positive) has ranged from
10% to 40% among adults seeking treatment in STD clinics
(62–64) and from 10% to 25% among MSM aged <30 years
(65; CDC, unpublished data, 1999–2000). Follow-up stud­
ies identified HBV infection in 20%–42% of susceptible het­
erosexual partners of persons with acute hepatitis B (66–68).
Among susceptible heterosexual spouses of persons with
chronic HBV infection, the seroprevalence of HBV infection
ranged from 25% to 59% (69–71).
Injection-drug users. IDUs account for approximately 16%
of new HBV infections in the United States (CDC, unpub­
lished data, 2001–2005). Incidence of HBV infection among
unvaccinated IDUs is high, ranging from 10 to 31 per 100
person-years (72–74). Risk for HBV transmission increases
with the number of years of drug use and is associated with
frequency of injection and with sharing of drug-preparation
equipment (e.g., cottons, cookers, and rinse water), indepen­
dent of syringe sharing (73,75).
In a study of the seroprevalence of HBV infection among
IDUs admitted to drug treatment in six U.S. cities, 64%
(range: 50%–81%) had serologic evidence of HBV infection,
and seroprevalence increased with age (76). Studies of
street-recruited IDUs (77,78) and female IDUs (79) have iden­
Vol. 55 / RR-16
Recommendations and Reports
tified similar prevalence of HBV infection, whereas a lower
prevalence (25%) was found in a study of young IDUs (aged
18–30 years) (74). Chronic HBV infection has been identi­
fied in 3.1% of IDUs in a detention setting (77) and 7.1% of
IDUs with HIV coinfection (80).
Household contacts of persons with chronic HBV infec­
tion. Seroprevalence of HBV infection among susceptible
household contacts of persons with chronic infection has var­
ied, ranging from 14% to 60% (69,71,81–85). The risk for
infection is highest among sex partners of, and children living
with, a person with chronic HBV infection in a household or
extended family setting (83–85).
Developmentally disabled persons in long-term–care
facilities. Developmentally disabled persons in residential and
nonresidential facilities historically have had high rates of HBV
infection (86,87), but the prevalence of infection has declined
substantially since the implementation of routine hepatitis B
vaccination in these settings (88,89). Nonetheless, because
HBsAg-positive persons reside in such facilities, clients and
staff continue to be at risk for infection.
Persons at risk for occupational exposure to HBV.
Before hepatitis B vaccination was widely implemented, HBV
infection was recognized as a common occupational hazard
among persons who were exposed to blood while caring for
patients or working in laboratories (90,91). Since then, rou­
tine hepatitis B vaccination of health-care workers and use of
standard precautions to prevent exposure to bloodborne patho­
gens have made HBV infection a rare event in these popula­
tions (92–94). Since the mid-1990s, the incidence of HBV
infection among health-care workers has been lower than that
among the general population (94). Public safety workers with
exposures to blood also might be at risk for HBV infection
(95–97); however, the prevalence of HBV infection in occu­
pational groups such as police officers, firefighters, and cor­
rections officers generally does not differ from that in the
general population when adjusted for race and age (97), and
infection is associated most often with nonoccupational risk
factors (97,98). No increased risk for occupationally acquired
HBV infection has been documented in workers exposed
infrequently to blood or body fluids (e.g., ward clerks, dietary
workers, maintenance workers, housekeeping personnel, teach­
ers, and persons employed in day care settings) (91).
Hemodialysis patients. Since the initiation of strict infec­
tion-control practices and hepatitis B vaccination, the rate of
HBV infection among patients undergoing hemodialysis has
declined approximately 95% (99,100). Nonetheless, repeated
outbreaks of HBV infection among unvaccinated patients
underscore the continued risk for infection in this population (101).
7
Persons with chronic liver disease. Persons with chronic
liver disease are not at increased risk for HBV infection unless
they have percutaneous or mucosal exposure to infectious
blood or body fluids. Furthermore, studies of the outcomes
of acute hepatitis B among patients with chronic liver disease
provide little evidence that acute hepatitis B increases their
risk for an acute liver failure. However, concurrent chronic
HBV infection might increase the risk for progressive chronic
liver disease in HCV-infected patients (102).
Travelers to HBV-endemic regions. Short-term travelers
to regions in which HBV infection is of high or intermediate
endemicity (Box 2) typically are at risk for infection only
through exposure to blood in medical, health-care, or disasterrelief activities; receipt of medical care that involves parenteral
exposures; or sexual activity or drug use (103). Infection rates
of 2%–5% per year among persons working in such regions
for >6 months have been reported (104,105).
HIV-positive persons. Published data on the overall preva­
lence of HBV and HIV coinfection in the United States are
BOX 2. Geographic regions* with intermediate† and high§
hepatitis B virus endemicity
Africa: all countries
East Asia: all countries
Eastern Europe and Northern Asia: all countries
except Hungary
South Asia: all countries except Sri Lanka
Southeast Asia: all countries
Australia and the South Pacific: all countries and
territories except Australia and New Zealand
Middle East: all countries except Cyprus
Western Europe: Greece, Malta, Portugal, and Spain
and indigenous populations of Greenland
North America: Alaska Natives and indigenous
populations of Northern Canada
Central America: Belize, Guatemala, Honduras, and
Panama
South America: Argentina, Bolivia, Brazil, Ecuador, Guyana,
Suriname, Venezuela, and the Amazonian areas of
Colombia and Peru
Caribbean: Antigua and Barbuda, Dominica,
Dominican Republic, Grenada, Haiti, Jamaica, Puerto
Rico, St. Kitts and Nevis, St. Lucia, St. Vincent and
Grenadines, Trinidad and Tobago, and Turcs and
Caicos
* A complete list of countries in each region is available at http://www.cdc.
gov/travel/destinat.htm.
† Hepatitis B surface antigen (HBsAg) prevalence of 2%–7%.
§ HBsAg prevalence of >8%.
MMWR
limited. Studies of certain subgroups have identified prevalence
of previous or current HBV infection of 45% in HIV-infected
MSM aged 22–29 years (CDC, unpublished data, 1998–2000),
24% in adolescent HIV-infected males (106), and 43% in HIVinfected women, including 76% among HIV-infected female
IDUs (79). Chronic HBV infection has been identified in
6%–14% of HIV-positive persons from Western Europe and
the United States, including 9%–17% of MSM, 7%–10% of
IDUs, and 4%–6% of heterosexuals (107).
The course of HBV infection can be modified in the pres­
ence of HIV, with a lower incidence of jaundice and a higher
incidence of chronic HBV infection (20,108,109). Limited
data also indicate that HIV-infected patients with chronic HBV
infection have an increased risk for liver-related mortality and
morbidity (110).
20
Black, non-Hispanic
Asian/Pacific Islander
American Indian/Alaska Native
15
Hispanic
White, non-Hispanic
10
5
0
1990
Incidence of Acute Hepatitis B
1995
2000
2005
Year
During 1990–2005, the overall incidence of reported acute
hepatitis B declined 78%, from 8.5 to 1.9 per 100,000 popu­
lation (Figure 2), and the estimated number of new HBV
infections, after adjusting for underreporting and asymptom­
atic infections, declined from approximately 232,000 to
approximately 51,000 infections (CDC, unpublished data,
1990–2005). Among children and adolescents aged <19 years,
incidence declined 96%, from 2.4 to 0.1 per 100,000 popu­
lation. Among adults aged >19 years, incidence declined 76%,
from 9.9 to 2.4 per 100,000 population, and racial/ethnic
disparities in incidence were nearly eliminated for Asians/
Pacific Islanders, American Indians/Alaska Natives, and His­
panics (Figure 3). Incidence also declined substantially among
blacks aged >19 years during this period, from 19.7 to 4.2 per
100,000 population; however, in 2005, incidence among
blacks remained nearly three times higher than that among
other racial/ethnic populations. After leveling during 1999–
FIGURE 2. Reported incidence* of acute hepatitis B, by age
group — United States, 1990–2005
15
>20 yrs
12–19 yrs
Incidence
December 8, 2006
FIGURE 3. Reported incidence* of acute hepatitis B among
persons aged >19 years, by race/ethnicity — United States,
1990–2005
Incidence
8
<12 yrs
10
* Per 100,000 population.
2002, acute hepatitis B incidence among adults decreased 35%
during 2002–2005, from 3.7 to 2.4 per 100,000 population
(CDC, unpublished data, 2006). In 2005, the highest inci­
dence of acute hepatitis B occurred among persons aged
25–44 years.
Prevalence of HBV Infection
During 1988–1994, the overall age-adjusted prevalence of
HBV infection (including previous or chronic infection) in
the U.S. population was 4.9%, and the prevalence of chronic
infection was 0.4% (111). Persons who have immigrated to
the United States from countries in which HBV is endemic
(Box 2, Figure 4) are affected disproportionately by chronic
HBV infection; in particular, the majority of chronic HBV
infections in the United States are among Asians/Pacific
Islanders (112–114). The prevalence of chronic HBV infec­
tion among persons immigrating to the United States from
Central and Southeast Asia, the Middle East, and Africa var­
ies (range: 5%–15%) and reflects the patterns of HBV infec­
tion in the countries and regions of origin. During 1994–2003,
approximately 40,000 immigrants with chronic HBV infec­
tion were admitted annually to the United States for perma­
nent residence (115; CDC, unpublished data, 2005).
5
Prophylaxis Against HBV Infection
0
1990
1995
2000
Year
* Per 100,000 population.
2005
Hepatitis B Vaccine
Hepatitis B vaccine is available as a single-antigen formula­
tion and also in fixed combination with other vaccines. Two
Vol. 55 / RR-16
Recommendations and Reports
9
FIGURE 4. Geographic distribution of chronic hepatitis B virus (HBV) infection — worldwide, 2005*
HBsAg prevalence
>8% = high
2%–7% = intermediate
<2% = low
* For multiple countries, estimates of prevalence of hepatitis B surface antigen (HBsAg), a marker of chronic HBV infection, are based on limited data and
might not reflect current prevalence in countries that have implemented childhood hepatitis B vaccination. In addition, HBsAg prevalence might vary
within countries by subpopulation and locality.
single-antigen vaccines are available in the United States:
Recombivax HB® (Merck & Co., Inc., Whitehouse Station,
New Jersey) and Engerix-B® (GlaxoSmithKline Biologicals,
Rixensart, Belgium). Of the three licensed combination vac­
cines, one (Twinrix® [GlaxoSmithKline Biologicals, Rixensart,
Belgium]) is used for vaccination of adults and two (Comvax®
[Merck & Co., Inc., Whitehouse Station, New Jersey] and
Pediarix® [GlaxoSmithKline Biologicals, Rixensart, Belgium])
are used for vaccination of infants and young children. Twinrix
contains recombinant HBsAg and inactivated hepatitis A virus.
Comvax contains recombinant HBsAg and Haemophilus
influenzae type b (Hib) polyribosylribitol phosphate conju­
gated to Neisseria meningitidis outer membrane protein com­
plex. Pediarix contains recombinant HBsAg, diphtheria and
tetanus toxoids and acellular pertussis adsorbed (DTaP), and
inactivated poliovirus (IPV).
HBsAg is the antigen used for hepatitis B vaccination
(116,117). Vaccine antigen can be purified from the plasma
of persons with chronic HBV infection or produced by
recombinant DNA technology. For vaccines available in the
United States, recombinant DNA technology is used to
express HBsAg in yeast, which then is purified from the cells
by biochemical and biophysical separation techniques
(118,119). Hepatitis B vaccines licensed in the United States
are formulated to contain 10–40 µg of HBsAg protein/mL.
Hepatitis B vaccines produced for distribution in the United
States do not contain thimerosal as a preservative or contain
only a trace amount (<1.0 µg mercury/mL) from the manu­
facturing process (120,121).
Hepatitis B Immune Globulin
HBIG provides passively acquired anti-HBs and temporary
protection (i.e., 3–6 months) when administered in standard
doses. HBIG typically is used as an adjunct to hepatitis B
vaccine for postexposure immunoprophylaxis to prevent HBV
infection. For nonresponders to hepatitis B vaccination, HBIG
administered alone is the primary means of protection after
an HBV exposure.
HBIG is prepared from the plasma of donors with high
concentrations of anti-HBs. The plasma is screened to elimi­
nate donors who are positive for HBsAg, antibodies to HIV
10
MMWR
and hepatitis C virus (HCV), and HCV RNA. In addition,
proper manufacturing techniques for HBIG inactivate viruses
(e.g., HBV, HCV, and HIV) from the final product (122,123).
No evidence exists to indicate that HBV, HCV, or HIV ever
has been transmitted by HBIG commercially available in the
United States. HBIG that is commercially available in the
United States does not contain thimerosal.
Adult Vaccination Schedules
and Results of Vaccination
Preexposure Vaccination
Vaccination of Adults
Primary vaccination consists of >3 intramuscular doses of
hepatitis B vaccine (Table 2). The 3-dose vaccine series
administered intramuscularly at 0, 1, and 6 months produces
a protective antibody response in approximately 30%–55%
of healthy adults aged <40 years after the first dose, 75% after
the second dose, and >90% after the third dose (124,125).
After age 40 years, the proportion of persons who have a pro­
tective antibody response after a 3-dose vaccination regimen
declines below 90%, and by age 60 years, protective levels of
antibody develop in only 75% of vaccinated persons (126).
In addition to age, other host factors (e.g., smoking, obesity,
genetic factors, and immune suppression) contribute to
decreased vaccine response (127–130). Alternative vaccina­
tion schedules (e.g., 0, 1, and 4 months or 0, 2, and 4 months)
have been demonstrated to elicit dose-specific and final rates
of seroprotection similar to those obtained on a 0-, 1-,
6-month schedule (131).
The combined hepatitis A–hepatitis B vaccine (Twinrix) is
indicated for vaccination of persons aged >18 years with risk
factors for both hepatitis A and hepatitis B. The dosage of the
December 8, 2006
hepatitis A component in the combined vaccine is lower than
that in the single-antigen hepatitis A vaccine, allowing it to be
administered in a 3-dose schedule instead of the 2-dose sched­
ule used for the single-antigen vaccine.
Nonstandard Vaccine Schedules
No apparent effect on immunogenicity has been docu­
mented when minimum spacing of doses (i.e., 4 weeks
between doses 1 and 2, 8 weeks between doses 2 and 3, and
16 weeks between doses 1 and 3) is not achieved precisely.
Increasing the interval between the first 2 doses has little
effect on immunogenicity or final antibody concentration
(132–134). The third dose confers the maximum level of
seroprotection but acts primarily as a booster and appears to
provide optimal long-term protection (135). Longer intervals
between the last 2 doses result in higher final antibody levels
but might increase the risk for acquisition of HBV infection
among persons who have a delayed response to vaccination.
No differences in immunogenicity are observed when vac­
cines from different manufacturers are used to complete the
vaccine series.
Response to Revaccination
Although serologic testing for immunity is not necessary
after routine vaccination of adults, postvaccination testing is
recommended for persons whose subsequent clinical manage­
ment depends on knowledge of their immune status, includ­
ing certain health-care and public safety workers; chronic
hemodialysis patients, HIV-infected persons, and other
immunocompromised persons; and sex or needle-sharing part­
ners of HBsAg-positive persons (Appendix A). Of persons who
did not respond to a primary 3-dose vaccine series with antiHBs concentrations of >10 mIU/mL, 25%–50% responded
to an additional vaccine dose, and 44%–100% responded to
a 3-dose revaccination series (136–141). Better response to
TABLE 2. Recommended doses of currently licensed formulations of adult hepatitis B vaccine, by group and vaccine type
Single-antigen vaccine
Recombivax HB®*
Combination vaccine
Engerix-B®†
Twinrix®†§
Dose
(µg)¶
Vol.
(mL)
Dose
(µg)¶
Vol.
(mL)
Dose
(µg)¶
Vol.
(mL)
Adults (aged >20 years)
10
1.0
20
1.0
20
1.0
Hemodialysis patients and other immunocompromised
persons aged >20 yrs
40**
1.0
40††
2.0
NA§§
Group
NA
* Merck & Co., Inc., Whitehouse Station, New Jersey.
† GlaxoSmithKline Biologicals, Rixensart, Belgium.
§ Combined hepatitis A and hepatitis B vaccine, recommended for persons aged >18 years who are at increased risk for both hepatitis B virus and
hepatitis A virus infections.
¶ Recombinant hepatitis B surface antigen protein dose.
** Dialysis formulation administered on a 3-dose schedule at 0, 1, and 6 months.
†† Two 1.0-mL doses administered in 1 or 2 injections on a 4-dose schedule at 0, 1, 2, and 6 months.
§§ Not applicable.
Vol. 55 / RR-16
Recommendations and Reports
revaccination occurs in persons who have measurable but low
(<10 mIU/mL) levels of antibody after the initial series
(136,137). Increased vaccine doses (e.g., double the standard
dose) were demonstrated to enhance revaccination response
rates in one study (140) but not in another (138). Intrader­
mal vaccination has been reported to be immunogenic in per­
sons who did not respond to intramuscular vaccination
(142,143); however, intradermal vaccination is not a route of
administration indicated in the manufacturers’ package label­
ing. Persons who do not have protective levels of anti-HBs
1–2 months after revaccination either are primary
nonresponders or are infected with HBV. Genetic factors might
contribute to nonresponse to hepatitis B vaccination
(130,137).
Groups Requiring Different Vaccination Doses
or Schedules
Compared with immunocompetent adults, hemodialysis
patients are less likely to have protective levels of antibody
after vaccination with standard vaccine dosages; protective
levels of antibody developed in 67%–86% (median: 64%) of
adult hemodialysis patients who received 3–4 doses of either
vaccine in various dosages and schedules (100). Higher
seroprotection rates have been identified in patients with
chronic renal failure, particularly those with mild or moder­
ate renal failure, who were vaccinated before becoming dialy­
sis dependent. After vaccination with a 4-dose series, the
seroprotection rate among adult predialysis patients with
serum creatinine levels of <4.0 mg/dL was 86%, compared
with 37% among patients with serum creatinine levels of >4.0
mg/dL, 88% of whom were dialysis patients (144).
Humoral response to hepatitis B vaccination also is reduced
in other immunocompromised persons (e.g., HIV-infected
persons, hematopoietic stem-cell transplant recipients, and
patients undergoing chemotherapy) (145–147). Modified
dosing regimens, including doubling the standard antigen dose
or administering additional doses, might increase response rates
(148–150). However, limited data regarding response to these
alternative vaccination schedules are available.
Immune Memory
Anti-HBs is the only easily measurable correlate of vaccineinduced protection. Immunocompetent persons who achieve
anti-HBs concentrations of >10 mIU/mL after preexposure
vaccination have nearly complete protection against both acute
disease and chronic infection, even if anti-HBs concentrations
decline subsequently to <10 mIU/mL (151–154). Although
immunogenicity is lower among immunocompromised per­
sons, those who achieve and maintain a protective antibody
11
response before exposure to HBV have a high level of protec­
tion from infection (155,156).
After primary immunization with hepatitis B vaccine, antiHBs levels decline rapidly within the first year and more slowly
thereafter. Among young adults who respond to a primary
vaccine series with antibody concentrations of >10 mIU/mL,
17%–50% have low or undetectable concentrations of antiHBs (reflecting anti-HBs loss) 10–15 years after vaccination
(155–157). In the absence of exposure to HBV, the persis­
tence of detectable anti-HBs after vaccination depends on the
concentration of postvaccination antibodies (158).
Even when anti-HBs concentrations decline to <10 mIU/mL,
nearly all vaccinated persons remain protected against HBV
infection. The mechanism for continued vaccine-induced pro­
tection is thought to be the preservation of immune memory
through selective expansion and differentiation of clones of
antigen-specific B and T lymphocytes (159). Persistence of
vaccine-induced immune memory among persons who
responded to a primary adult vaccine series 4–23 years previ­
ously but then had anti-HBs concentrations of <10 mIU/mL
has been demonstrated by an anamnestic increase in anti-HBs
concentrations in 74%–100% of these persons 2–4 weeks
after administration of an additional vaccine dose and by
antigen-specific B and T cell proliferation (160). Although
direct measurement of immune memory is not yet possible,
these data indicate that a high proportion of vaccinees retain
immune memory and would have an anti-HBs response upon
exposure to HBV.
Population-based studies of highly vaccinated populations
have demonstrated elimination of new HBV infections for up
to 2 decades after hepatitis B immunization programs were
initiated (161–163). Breakthrough infections (detected by the
presence of anti-HBc or HBV DNA) have been documented
in a limited percentage of vaccinated persons (159,164), but
these infections typically are transient and asymptomatic;
breakthrough infections resulting in chronic HBV infection
have been documented only rarely among infants born to
HBsAg-positive mothers (165) and have not been observed
among immunocompetent adults.
Limited data are available on the duration of immune
memory after hepatitis B vaccination in immunocompromised
persons (e.g., HIV-infected patients, dialysis patients, patients
undergoing chemotherapy, or hematopoietic stem-cell trans­
plant patients). No clinically significant HBV infections have
been documented among immunocompromised persons who
maintain protective levels of anti-HBs. In studies of long-term
protection among HIV-infected persons, breakthrough infec­
tions occurring after a decline in anti-HBs concentrations to
<10 mIU/mL have been transient and asymptomatic (155).
12
MMWR
However, among hemodialysis patients who responded to the
vaccine, clinically significant HBV infection has been docu­
mented in persons who have not maintained anti-HBs con­
centrations of >10 mIU/mL (166).
December 8, 2006
However, in placebo-controlled studies, these side effects were
reported no more frequently among persons receiving hepati­
tis B vaccine than among persons receiving placebo (179).
Adverse Events
Postexposure Prophylaxis
Both passive-active postexposure prophylaxis (PEP) using
HBIG and hepatitis B vaccine and active PEP using hepatitis
B vaccine alone are highly effective in preventing infection
after exposure to HBV (167–170). HBIG alone has also been
demonstrated to be effective in preventing HBV transmission
(68,171–173), but with the availability of hepatitis B vac­
cine, HBIG typically is used as an adjunct to vaccination.
Guidelines for PEP for adults with occupational (174) and
nonoccupational exposures (Appendix B) to HBV have been
developed.
The major determinant of the effectiveness of PEP is early
administration of the initial dose of vaccine. The effectiveness
of PEP diminishes the longer after exposure it is initiated
(27,175,176). Studies are limited on the maximum interval
after exposure during which PEP is effective, but the interval
is likely <7 days for needlestick (171,172,177) exposures and
<14 days for sexual exposures (68,154,168,170,173).
Substantial evidence suggests that adults who respond to
hepatitis B vaccination are protected from chronic HBV
infection for at least 20 years even if vaccinees lack detectable
anti-HBs at the time of an exposure (151–153). For this rea­
son, immunocompetent persons who have had postvaccina­
tion testing and are known to have responded to hepatitis B
vaccination with anti-HBs concentrations of >10 mIU/mL
do not require additional passive or active immunization after
an HBV exposure and do not need further periodic testing to
assess anti-HBs concentrations.
Vaccine Safety
Hepatitis B vaccines have been demonstrated to be safe when
administered to infants, children, adolescents, and adults
(178). Since 1982, an estimated 70 million adolescents and
adults and 50 million infants and children in the United States
have received >1 dose of hepatitis B vaccine (CDC, unpub­
lished data, 2004).
Vaccine Reactogenicity
The most frequently reported side effects in persons receiv­
ing hepatitis B vaccine are pain at the injection site (3%–29%)
and temperature of >99.9°F (>37.7°C) (1%–6%) (124,125).
CDC and FDA continually assess the safety of hepatitis B
vaccine and other vaccines through ongoing monitoring of
data from the Vaccine Safety Datalink (VSD) project, the
Vaccine Adverse Events Reporting System (VAERS), and other
surveillance systems. A causal association has been established
between receipt of hepatitis B vaccine and anaphylaxis (178).
On the basis of VSD data, the estimated incidence of anaphy­
laxis among children and adolescents who received hepatitis
B vaccine is one case per 1.1 million vaccine doses distributed
(95% confidence interval = 0.1–3.9) (180).
Early postlicensure surveillance of adverse events suggested
a possible association between Guillain-Barré syndrome (GBS)
and receipt of the first dose of plasma-derived hepatitis B vac­
cine among U.S. adults (181). However, in a subsequent analy­
sis of GBS cases reported to CDC, FDA, and vaccine
manufacturers, among an estimated 2.5 million adults who
received >1 dose of recombinant hepatitis B vaccine during
1986–1990, the rate of GBS that occurred after hepatitis B
vaccination did not exceed the background rate among
unvaccinated persons (CDC, unpublished data, 1992). An
Institute of Medicine review concluded that evidence was
insufficient to reject or accept a causal association between
GBS and hepatitis B vaccination (178,182,183).
One retrospective case-control study (184,185) reported an
association between hepatitis B vaccine and multiple sclerosis
(MS) among adults. However, multiple studies (186–189) have
demonstrated no such association. Reviews by scientific pan­
els have favored rejection of a causal association between hepa­
titis B vaccination and MS (190,191).
In rare instances, chronic illnesses have been reported after
hepatitis B vaccination, including chronic fatigue syndrome
(192), neurologic disorders (e.g., leukoencephalitis, optic neu­
ritis, and transverse myelitis) (193–195), rheumatoid arthri­
tis (196,197), type 1 diabetes (198), and autoimmune disease
(199). However, no evidence of a causal association between
these conditions or other chronic illnesses and hepatitis B vac­
cine has been demonstrated (183,190,200–203).
Reported episodes of alopecia (hair loss) after rechallenge
with hepatitis B vaccine suggest that vaccination might, in
rare cases, trigger episodes of alopecia (204). However, a popu­
lation-based study determined no statistically significant
association between alopecia and hepatitis B vaccine (205).
Vol. 55 / RR-16
Recommendations and Reports
Contraindications and Precautions
Hepatitis B vaccination is contraindicated for persons with
a history of hypersensitivity to yeast or any vaccine compo­
nent (206–209). Despite a theoretic risk for allergic reaction
to vaccination in persons with allergy to Saccharomyces cerevisiae
(baker’s yeast), no evidence exists to document adverse reac­
tions after vaccination of persons with a history of yeast allergy.
Persons with a history of serious adverse events (e.g., anaphy­
laxis) after receipt of hepatitis B vaccine should not receive
additional doses. As with other vaccines, vaccination of persons
with moderate or severe acute illness, with or without fever,
should be deferred until illness resolves (210). Vaccination is
not contraindicated in persons with a history of MS, GBS,
autoimmune disease (e.g., systemic lupus erythematosis or rheu­
matoid arthritis), or other chronic diseases.
Pregnancy is not a contraindication to vaccination. Limited
data suggest that developing fetuses are not at risk for adverse
events when hepatitis B vaccine is administered to pregnant
women (211). Available vaccines contain noninfectious HBsAg
and should cause no risk of infection to the fetus.
Implementation Barriers
and Rationale for New
Recommendations
Soon after hepatitis B vaccine was licensed in 1982, ACIP
recommended vaccination for adults at increased risk for HBV
infection (212). However, the recommendations were not
widely implemented, and coverage among adults at risk for
HBV infection remained low. By the early 1990s, the diffi­
culty in vaccinating adults at risk for HBV infection and the
substantial burden of HBV-related disease resulting from
infections acquired during childhood indicated that additional
hepatitis B vaccination strategies were needed (213,214). In
1991, recommendations for vaccination of unvaccinated adults
at high risk for HBV infection became part of the national
strategy adopted by ACIP and professional medical organiza­
tions to eliminate HBV transmission in the United States (3).
However, hepatitis B vaccine still is not offered routinely in
medical settings serving adults, and a substantial number of
adults at risk for HBV infection remain unvaccinated.
Multiple factors contribute to low hepatitis B vaccination
coverage among adults at risk. In contrast to vaccination of
children, no national program exists to support vaccine pur­
chase and infrastructure for vaccine delivery to uninsured and
underinsured adults. Reimbursement mechanisms for vacci­
nation of adults with health insurance also are not widely used.
In addition, certain patients and health-care providers are
13
reluctant to discuss risk behaviors (215), and providers might
not make hepatitis B vaccination a priority compared with
other clinical care services.
One strategy demonstrated to be effective at increasing vac­
cination coverage among adults at risk for HBV infection is
to offer vaccination to all adults as part of routine prevention
services in settings in which a high proportion of adults have
HBV risk factors (10,216–223). In STD and HIV treatment
facilities, health-care settings serving IDUs, and health-care
settings targeting services to MSM, nearly all patients have
behavioral risk factors for HBV infection. Furthermore, a high
proportion of persons receiving health care in HIV testing
facilities or correctional facilities report sexual and drug-use
risk behaviors (224,225). Therefore, providing hepatitis B
vaccination in these settings offers an efficient and effective
way to reach adults at highest risk. During 2001–2004, in a
study of 760 adults with reported acute hepatitis B who par­
ticipated in CDC’s Sentinel Counties Study of Viral Hepati­
tis, 39% reported a history of STD treatment, 40% reported
a history of incarceration, and 22% reported a history of drug
treatment; overall, 61% would have had at least one opportu­
nity to be vaccinated either during STD or drug treatment or
at a correctional facility (226).
Demonstration projects that supported the purchase of hepa­
titis B vaccine and its administration in settings in which a
high proportion of adults have HBV risk factors have estab­
lished the feasibility of providing the vaccine as part of com­
prehensive STD, HIV, and hepatitis prevention services (10).
When clients were offered hepatitis B vaccination in such set­
tings, first-dose acceptance rates of 70%–85% were achieved
(10,216,223,227). These demonstration projects have identi­
fied the components of successful adult hepatitis B vaccina­
tion programs (Box 3). In addition, “one-stop” delivery of
integrated prevention services was preferred by the majority
of patients and typically resulted in enhanced delivery of all
BOX 3. Components of a successful adult hepatitis B vac­
cination program
• Institutional commitment to the program
• Trained and knowledgeable staff who promote the pro­
gram
• Patients who are informed about hepatitis B and the
health benefits of hepatitis B vaccination
• Integrated delivery of vaccination and other services
• Protocols and standing orders
• Protected patient confidentiality
• Infrastructure that ensures vaccine administration is
accessible, convenient, and flexible for patients
• Funding for vaccine
14
MMWR
prevention services (227). Return visits for second and third
doses of hepatitis B vaccine also provide opportunities for
patients to receive other STD/HIV-related services (e.g., test
results, additional counseling, and referral). Multiple studies
have established the cost-effectiveness of providing hepatitis
B vaccination at STD/HIV counseling and testing sites, cor­
rectional institutions, drug-abuse treatment centers, and other
settings serving adults at risk for HBV infection (228–231).
Universal vaccination of adults in settings in which a high
proportion of persons have HBV risk factors will reach a sub­
stantial proportion of all adults at risk for HBV infection.
However, not all adults with risk factors for HBV infection
visit these settings. For example, an estimated 80%–95% of
STDs are diagnosed in settings other than STD clinics
(232,233). Therefore, primary care and clinical preventive
service providers (e.g., physicians’ offices, community health
centers, family planning clinics, liver disease clinics, and travel
clinics) also should provide hepatitis B vaccine whenever
indicated or requested as part of regular preventive care. Lim­
ited data are available regarding best practices in primary care
and specialty medical settings to achieve high vaccination cov­
erage among adults at risk for HBV infection. In one project
in which hepatitis B vaccine was made available free of charge
to primary care clients in community clinics, low vaccination
coverage rates were observed, compared with rates at other
venues (10). This finding suggests that provision of free vac­
cine alone might not ensure increased use of hepatitis B vac­
cine and that other implementation strategies (e.g., education
and training of clinicians and standing orders) are needed to
prompt providers to offer vaccination to adults.
In primary care settings, targeting vaccination to persons at
risk is an efficient approach to preventing HBV infection.
During 2001–2005, among persons with acute hepatitis B
who participated in CDC’s Sentinel Counties Study of Viral
Hepatitis, 84% reported risk behaviors or characteristics,
either during the incubation period (i.e., 6 weeks–6 months)
or during their lifetimes, that placed them in a group for which
hepatitis B vaccination was recommended (CDC, unpublished
data, 2001–2005). Providers in primary care settings can
ascertain patients’ risks for HBV infection and identify candi­
dates for hepatitis B vaccination during routine patient visits.
Assessment of patients’ sex- and drug-related risk factors is
recommended by the U.S. Preventive Services Task Force and
the American Medical Association (AMA) (234,235) and has
the ancillary benefit of identifying candidates for other pre­
vention interventions (e.g., screening for HIV infection and
other STDs and drug-abuse treatment).
However, risk-targeted approaches can miss persons in need
of prevention services. Patients might be reluctant to report sex-
December 8, 2006
and drug-related behaviors, particularly when these behaviors are
not perceived as relevant to the clinical encounter. In addition,
despite recommendations of the U.S. Preventive Services Task
Force and AMA, providers might be reluctant to inquire about
behavioral risk factors. For example, surveys of physicians and
patients conducted during 1995–1999 indicated that fewer than
half of patients were asked about sexual behaviors (236–238).
Health-care providers should educate all patients about the
health benefits of hepatitis B vaccination, including risk factors
for HBV infection and the importance of vaccination for per­
sons who engage in certain risk behaviors. This information
might stimulate patients to request vaccination from their pri­
mary care providers, without requiring them to acknowledge a
specific risk factor.
Another possible strategy is to offer vaccination to all adults
in age groups with the highest incidence of infection as part
of routine medical care (Figure 1). An age-based approach
might simplify vaccination-related decision-making by prac­
titioners and remove the stigma associated with disclosure of
risk behaviors. Other adult vaccines, including those for
influenza and pneumococcal disease, are delivered on age-based
schedules. However, the effectiveness of age-based strategies
in increasing hepatitis B vaccination coverage among adults
at risk is unknown. In addition, age-based strategies for adult
vaccination would be substantially more costly than risktargeted approaches (CDC, unpublished data, 2005).
Lack of funding for vaccine and its administration is a
major barrier to provision of hepatitis B vaccine to adults.
Hepatitis B vaccine often is a reimbursable charge in healthcare settings that bill insurance or Medicaid for services, and
surveys of public and private insurers indicate high rates of
coverage for hepatitis B vaccination (239,240). In one study,
an estimated 74% of adults aged 18–49 years with risk factors
for HBV infection had health insurance coverage (241). How­
ever, public clinics might not have systems in place to bill for
vaccination services, and reimbursement of private providers
might be inadequate to cover the purchase and administra­
tion of vaccine. Other adults either lack private insurance or
are not eligible for reimbursement by Medicaid. Although the
Vaccines for Children program provides federally funded vac­
cine and administration costs for vaccination of uninsured
and underinsured children and youth aged <19 years, no simi­
lar program supports adult vaccination.
Certain adult hepatitis B vaccination programs have been
successful at identifying federal, state, or local funds to
provide free or low-cost hepatitis B vaccination to uninsured
or underinsured adults. For example, the Immunization Grant
Program, created under Section 317 of the Public Health
Service Act, provides funding to state, local, and territorial
Vol. 55 / RR-16
Recommendations and Reports
public health agencies for vaccine purchase and vaccinationprogram operation (242). Section 317 funds can be used to
purchase childhood and adult vaccines, including adult hepa­
titis B vaccine. However, lack of adequate funding constrains
efforts to increase vaccination coverage among adults. To
maximize available resources for hepatitis B vaccination, pub­
lic and private health-care providers should become familiar
with insurance billing and reimbursement mechanisms that
can be used for hepatitis B vaccine. AMA billing and reim­
bursement guidelines are available at http://www.ama-assn.org/
ama1/pub/upload/mm/36/ama_hep_coding_trifo.pdf.
Although HBV infections are expected to decline as a result
of universal childhood immunization and increased vaccina­
tion of adults at risk, an estimated 1.25 million persons in the
United States are living with chronic HBV infection and
require essential prevention services and medical management.
In particular, Asians/Pacific Islanders in the United States have
a high prevalence of chronic HBV infection, representing a
major health disparity. Persons with chronic HBV infection
often are unaware of their infection status or do not receive
needed care. Few programs have been implemented to iden­
tify HBsAg-positive persons, provide or refer these persons
for appropriate medical management, and provide vaccina­
tion to their contacts (243). During delivery of hepatitis B
vaccination and provision of other preventive services, healthcare providers have opportunities to identify persons with
chronic HBV infection, refer them for counseling and man­
agement, and ensure that their susceptible contacts receive
vaccination. Guidelines to identify and manage HBsAg­
positive persons have been developed (Appendix C).
Implementation of the recommendations and strategies
outlined in this report and the companion ACIP recommen­
dations for infants, children, and adolescents (11) should lead
ultimately to the elimination of HBV transmission in the
United States. New information will have implications for this
effort, and adjustments and changes are expected to occur.
Recommendations
and Implementation Strategies
for Hepatitis B Vaccination of Adults
Recommendations
• Hepatitis B vaccination is recommended for all unvacci­
nated adults at risk for HBV infection and for all adults
requesting protection from HBV infection (Box 4).
Acknowledgment of a specific risk factor should not be a
requirement for vaccination.
15
BOX 4. Adults recommended to receive hepatitis B vaccination
Persons at risk for infection by sexual exposure
• Sex partners of hepatitis B surface antigen (HBsAg)­
positive persons
• Sexually active persons who are not in a long-term,
mutually monogamous relationship (e.g., persons with
more than one sex partner during the previous 6 months)
• Persons seeking evaluation or treatment for a sexually
transmitted disease
• Men who have sex with men
Persons at risk for infection by percutaneous or
mucosal exposure to blood
• Current or recent injection-drug users
• Household contacts of HBsAg-positive persons
• Residents and staff of facilities for developmentally
disabled persons
• Health-care and public safety workers with reasonably
anticipated risk for exposure to blood or bloodcontaminated body fluids
• Persons with end-stage renal disease, including
predialysis, hemodialysis, peritoneal dialysis, and home
dialysis patients
Others
• International travelers to regions with high or interme­
diate levels (HBsAg prevalence of >2%) of endemic HBV
infection (Figure 4, Box 2)
• Persons with chronic liver disease
• Persons with HIV infection
• All other persons seeking protection from HBV infection
• Providers should select the vaccine schedule they consider
necessary to achieve completion of the vaccine series
(Table 2, Box 5).
• Public health programs and primary care providers should
adopt strategies appropriate for the practice setting to
ensure that all adults at risk for HBV infection are offered
hepatitis B vaccine (Box 6).
BOX 5. Hepatitis B vaccine schedules for adults (aged >20
years)*
0, 1, and 6 months
0, 1, and 4 months
0, 2, and 4 months
0, 1, 2, and 12 months†
* All schedules are applicable to single-antigen hepatitis B vaccines;
Twinrix® (combined hepatitis A and hepatitis B vaccine) may be
administered at 0, 1, and 6 months.
† A 4-dose schedule of Engerix-B® is licensed for all age groups.
16
MMWR
December 8, 2006
BOX 6. Implementation strategies for adult hepatitis B
vaccination
BOX 7. Settings in which hepatitis B vaccination is recom­
mended for all adults
Settings in which a high proportion of persons have
risk factors for hepatitis B virus (HBV) infection
• Implement standing orders to administer hepatitis B vac­
cine as part of routine services to all adults who have
not completed vaccination.*
Primary care and specialty medical settings
• Implement standing orders to identify adults recom­
mended for hepatitis B vaccination and administer vac­
cination as part of routine services.
— Provide information to all adults regarding the
health benefits of hepatitis B vaccination, includ­
ing risk factors for HBV infection and persons for
whom vaccination is recommended.
— Help adults assess their need for vaccination by ob­
taining a history that emphasizes risks for sexual
transmission and percutaneous or mucosal expo­
sure to blood.
— Administer hepatitis B vaccine to all adults who re­
port risks for HBV infection.*
— Provide hepatitis B vaccine to all adults seeking pro­
tection from HBV infection. Acknowledgment of
a specific risk factor for HBV infection is not a re­
quirement for vaccination.
Occupational health programs
• Identify staff whose work-related activities involve expo­
sure to blood or other potentially infectious body fluids.
• Provide education to encourage vaccination.
• Implement active follow-up, with reminders to track
vaccine-series completion among persons receiving vac­
cination.
• Provide appropriate postvaccination testing 1–2 months
after vaccine-series completion.
• Sexually transmitted disease treatment facilities
• Human immunodeficiency virus testing and treatment
facilities
• Facilities providing drug-abuse treatment and preven­
tion services
• Health-care settings targeting services to injection-drug users
• Correctional facilities
• Health-care settings targeting services to men who have
sex with men
• Chronic-hemodialysis facilities and end-stage renal
disease programs
• Institutions and nonresidential day care facilities for
developmentally disabled persons
* In populations that have expected high rates of previous HBV infection,
prevaccination testing might reduce costs by avoiding vaccination of
persons who are already immune (see Appendix A, Prevaccination
Serologic Testing for Susceptibility).
Implementation Strategies
• In settings in which a high proportion of persons have
risk factors for HBV infection (Box 7)
— all adults should be assumed to be at risk for HBV
infection and should be offered hepatitis B vaccina­
tion if they have not completed a licensed hepatitis B
vaccine series;
— health-care providers should implement standing
orders (244) to administer hepatitis B vaccine as part
of routine services to adults who have not completed
the vaccine series and make hepatitis B vaccination a
standard component of evaluation and treatment for
STDs and HIV/AIDS (Table 3); and
— when feasible, hepatitis B vaccination should be
offered in outreach and other settings in which ser­
vices are provided to persons at risk for HBV infection
(e.g., needle-exchange programs, HIV testing sites,
HIV prevention programs, and homeless shelters).
• In primary care and specialty medical settings (e.g.,
physician’s offices, family planning clinics, community
health centers, liver disease clinics, and travel clinics), pro­
viders should implement standing orders to identify adults
recommended for hepatitis B vaccination and administer
vaccination as part of routine services. To ensure vaccina­
tion of persons at risk for HBV infection, health-care
providers should
— provide information to all adults regarding the health
benefits of hepatitis B vaccination, including the risk
factors for HBV infection and persons for whom
vaccination is recommended;
— help all adults assess their need for vaccination by
obtaining a history that emphasizes risks for sexual
transmission and percutaneous or mucosal exposure
to blood;
— administer hepatitis B vaccine to adults who report
risk factors for HBV infection; and
— provide hepatitis B vaccine to all adults requesting pro­
tection from HBV infection without requiring
acknowledgment of a specific risk factor.
• Occupational health programs should
— identify all staff whose work-related activities involve
exposure to blood or other potentially infectious body
fluids in a health-care, laboratory, public safety, or
institutional setting (including employees, students,
contractors, attending clinicians, emergency medical
technicians, paramedics, and volunteers);
— provide education to staff to encourage vaccination;
Vol. 55 / RR-16
Recommendations and Reports
17
TABLE 3. Recommended HIV/AIDS, sexually transmitted disease (STD), and viral hepatitis prevention services, by risk population
Risk population*
High-risk heterosexuals
Persons seeking STD evaluation or treatment
Recommended services
Hepatitis B vaccination
Testing for human immunodeficiency virus (HIV) infection†
Testing for syphilis, gonorrhea, and chlamydia, as clinically indicated§
Sexually active men not in a long-term,
mutually monogamous relationship
Hepatitis B vaccination
Annual testing for HIV infection†¶
Sexually active women not in a long-term,
mutually monogamous relationship
Hepatitis B vaccination**
Annual testing for HIV infection†¶
Annual testing for chlamydia (Note: also recommended for all sexually active females aged <25 yrs)§
Men who have sex with men (MSM)
All MSM
Sexually active MSM not in a long-term,
mutually monogamous relationship
Hepatitis A vaccination
Hepatitis B vaccination**
Hepatitis A vaccination
Hepatitis B vaccination**
Annual testing for HIV infection†
Annual testing for syphilis, gonorrhea, and chlamydia§
Hepatitis A vaccination††
Hepatitis B vaccination
Testing for hepatitis C virus infection§§
Annual testing for HIV infection†
Substance-abuse treatment¶¶
* Testing for HIV infection, chlamydia, gonorrhea, syphilis, and hepatitis B surface antigen also is recommended for pregnant women (CDC. Revised
recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. MMWR 2006;55[No. RR-14]; CDC. Sexually
transmitted diseases treatment guidelines. MMWR 2006;55[No. RR-11]; CDC. A comprehensive immunization strategy to eliminate transmission of
hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices [ACIP]. Part 1: immunization of
infants, children, and adolescents. MMWR 2005;54[No. RR-16]).
† CDC. Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. MMWR 2006;55(No. RR-14).
§ CDC. Sexually transmitted diseases treatment guidelines 2006. MMWR 2006;55(No. RR-11).
¶ HIV screening is recommended for all persons aged 13–64 years. Repeat screening is recommended at least annually for persons likely to be at high
risk for HIV infection, including MSM or heterosexuals who themselves or whose sex partners have had more than one partner since their most recent
HIV test.
** Hepatitis B vaccination is recommended for persons with more than one sex partner during the previous 6 months.
†† CDC. Prevention of hepatitis A through active or passive immunization: recommendations of the Advisory Committee on Immunization Practices
(ACIP). MMWR 2006;55(No. RR-7).
§§ CDC. Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease. MMWR 1998;47(No. RR-19).
Recommended frequency of testing for hepatitis C virus infection has not been determined.
¶¶ CDC. Substance abuse treatment for injection drug users: a strategy with many benefits. Atlanta, GA: US Department of Health and Human Services,
CDC; 2002. Available at http://www.cdc.gov/idu/facts/treatment.htm.
Injection-drug users
— implement active follow-up, with reminders to track
completion of the vaccine series among persons
receiving vaccination; and
— provide appropriate postvaccination testing
(Appendix A).
• Providers in all settings in which hepatitis B vaccine is
provided should
— assess patients’ needs for other vaccines recommended
for adults (schedule available at http://www.cdc.gov/
nip/recs/adult-schedule.htm) and administer these
vaccines at the same office visit at which hepatitis B
vaccine is administered;
— identify and vaccinate all susceptible household, sex,
and needle-sharing contacts of HBsAg-positive per­
sons, and provide HBsAg-positive persons with
appropriate referrals for counseling and medical man­
agement (Appendix C);
— provide culturally appropriate materials to educate
adults about hepatitis B and the importance of vacci­
nation (available at http://www.cdc.gov/ncidod/
diseases/hepatitis/b/index.htm#materials);
— offer vaccination in a way that is accessible, conve­
nient, and flexible for patients;
— be familiar with ACIP’s general recommendations on
immunization (210), which provide technical guid­
ance regarding common immunization concerns of
health-care providers;
— give persons who are eligible for vaccination a copy
of the most current vaccine information statement
for hepatitis B vaccine, as required by federal law
18
MMWR
(see Appendix A, Hepatitis B Vaccine Dose and
Administration);
— institute methods to identify persons with a history of
vaccination (see Appendix A, Unknown or Uncertain
Vaccination Status);
— provide vaccinated persons with a personal record
card documenting receipt of vaccination (available
at http://www.immunize.org/guide/aov21_appb_
record.pdf );
— develop tracking and reminder systems to ensure
completion of the vaccine series (descriptions of such
systems are available at http://www.cdc.gov/nip/
publications/adultstrat.htm);
— report adverse events to VAERS using report forms
and assistance available from CDC at telephone
1-800-822-7967 or from VAERS at http://www.vaers.
hhs.gov; and
— be familiar with billing and reimbursement guidelines
for hepatitis B vaccination (available at http://www.
ama-assn.org/ama1/pub/upload/mm/36/ama_hep_
coding_trifo.pdf ).
• Public health agencies and medical organizations should
educate providers about the benefits of hepatitis B vacci­
nation for their patients and methods to implement and
support hepatitis B vaccination services in their settings
and practices. Health departments and community-based
organizations should increase awareness of the benefits of
hepatitis B vaccination, particularly among persons at
increased risk for HBV infection. Educational materials
are available at http://www.cdc.gov/ncidod/diseases/
hepatitis/index.htm.
• Health departments are encouraged to implement adult
immunization registries to track the receipt of hepatitis B
vaccine in all settings in which adults are vaccinated.
Information on immunization registries is available at
http://www.cdc.gov/nip/registry.
• Although hepatitis B vaccination programs aim to achieve
the highest possible rate of vaccine series completion, con­
cerns regarding completion of the hepatitis B vaccine
series should not preclude initiation of hepatitis B vacci­
nation. Each dose of vaccine confers some protection
against HBV infection. Vaccine immunogenicity is not
decreased by lengthened intradose intervals, and the sec­
ond and third doses can be administered during subse­
quent health-care visits outside of the recommended
vaccine schedule.
December 8, 2006
Acknowledgments
The following persons contributed to the development of this
report: Guthrie S. Birkhead, MD, AIDS Institute, New York State
Department of Health, Albany, New York; Anna S. F. Lok, MD,
Division of Gastroenterology, University of Michigan, Ann Arbor,
Michigan; Molli C. Conti, Hepatitis B Foundation, Doylestown,
Pennsylvania; Josiah D. Rich, MD, Brown University, Providence,
Rhode Island; Robert A. Gunn, MD, San Diego County Health
and Human Services Agency, San Diego, California; Harold S.
Margolis, MD, Joanna Buffington, MD, Alison Greenspan, MPH,
Stephanie M. Neitzel, Kevin P. O’Connor, MA, Annemarie Wasley,
PhD, Brigette F. Ulin, MPH, Ian T. Williams, PhD, Division of
Viral Hepatitis, Matthew T. McKenna, MD, Division of HIV/AIDS
Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD,
and TB Prevention (proposed); William L. Atkinson, MD, Edward
W. Brink, MD, Immunization Services Division, Susan A. Maloney,
MD, Division of Global Migration and Quarantine, National
Center for Immunization and Respiratory Diseases (proposed),
CDC.
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26
MMWR
December 8, 2006
Appendix A
Immunization Management Issues
Hepatitis B Vaccine Dose
and Administration
• Recommended vaccine doses vary by product, age of
recipient, and needs of special populations (see Table 2).
Although the antigen contents of vaccines differ, vaccines
made by different manufacturers are interchangeable for
all adult schedules.
• Hepatitis B vaccine should be administered by intramus­
cular injection. The deltoid muscle is the recommended
site of administration for adults. Injection into the but­
tock is associated with decreased immunogenicity (1–4).
Intradermal administration can result in a lower sero­
conversion rate and final concentration of antibody to
hepatitis B surface antigen (anti-HBsAg) compared
with intramuscular administration; limited data are avail­
able to assess long-term protection from this route of
administration (5,6).
• For intramuscular injection, the needle should be long
enough to reach the muscle mass and prevent vaccine from
seeping into subcutaneous tissue, but not so long as to
involve underlying nerves and blood vessels or bone (7).
The appropriate needle length for adults is 1”–1½”
(25–38 mm), depending on the recipient’s weight
(1” [25 mm] for males and females weighing <60 kg
[<130 lbs]; 1”–1½” [25–38 mm] for females weighing
60–90 kg [130–200 lbs] and males weighing 60–118 kg
[130–260 lbs]; and 1½” [38 mm] for females weighing
>90 kg [>200 lbs] and males weighing >118 kg
[>260 lbs]). A 22- to 25-gauge needle should be used.*
• Hepatitis B vaccine administered by any route or site other
than intramuscularly in the deltoid muscle should not be
counted as valid and should be repeated unless serologic
testing indicates that an adequate response has been
achieved (see Postvaccination Testing for Serologic
Response).
• Hepatitis B vaccine and other vaccines administered during
the same visit should be given in different injection sites.
• For persons at risk for hemorrhage (e.g., persons with
hemophilia), the risk for bleeding after intramuscular
injection can be minimized by using a 23-gauge (or
smaller) needle, applying direct pressure to the injection
site for 1–2 minutes, and administering vaccine immedi­
* Certain experts recommend a 5/8” (16 mm) needle for males and females
weighing <60 kg (<130 lbs) (7).
ately after infusion of coagulation factor. Subcutaneous
administration of vaccine can be considered for these
persons but might result in lower response and increased
local reaction.
• Hepatitis B vaccine should be stored at 35°F–46°F
(2°C–8oC) and should not be frozen.
• A vaccine information statement (VIS) must be provided
to recipients of hepatitis B vaccine. The National Childhood
Vaccine Injury Act of 1986 (42 U.S.C. § 300aa-26)
requires vaccine providers to give a copy of the most cur­
rent vaccine-specific VIS to all recipients of vaccines that
are included on the National Vaccine Injury Compensa­
tion Program table maintained by the Health Resources
and Services Administration (available at http://www.hrsa.
gov). Hepatitis B vaccine is included on this table. The
most current VIS for hepatitis B vaccine is available at
http://www.cdc.gov/nip/publications/vis. Statements in
languages other than English are available from the
Immunization Action Coalition at http://www.immunize.org.
• Adverse events should be reported to the Vaccine Adverse
Events Reporting System; report forms and assistance are
available from CDC at telephone 1-800-822-7967 or at
http://www.vaers.hhs.gov.
Hepatitis B Immune Globulin (HBIG)
Dose and Administration
• The standard dose of HBIG is 0.06 mL/kg for all
applications in adults.
• HBIG may be administered simultaneously with
hepatitis B vaccine but in a different injection site.
• HBIG is administered by intramuscular injection. An
appropriate muscle mass (i.e., deltoid or gluteal) should
be chosen in which to deliver the large volumes of HBIG
required by using a needle length appropriate for the
person’s age and size (7).
• HBIG should be stored at 35°F–46°F (2°C–8°C) and
should not be frozen.
Unknown or Uncertain Vaccination
Status
• A reliable vaccination history is defined as a written, dated
record (e.g., personal, school, physician, or immuniza­
tion registry) of each dose of a complete series.
Vol. 55 / RR-16
Recommendations and Reports
• In the majority of clinical practice settings, providers
should accept only written and dated records as evidence
of vaccination. Although vaccinations should not be post­
poned if records cannot be located, providers should try
to locate missing records by contacting previous healthcare providers and asking patients to search for personally
held records. Persons whose records cannot be located
should be considered susceptible and started or continued
on the age-appropriate vaccine schedule.
• In settings in which written vaccination records are not
accessible (e.g., sexually transmitted disease [STD] treat­
ment facilities, human immunodeficiency virus [HIV]
testing facilities, or correctional facilities), an oral history
of completing a hepatitis B vaccine series can be used to
defer hepatitis B vaccination. Persons in these settings who
are uncertain about their vaccination status should be
vaccinated. Other methods for assessing vaccination his­
tory (e.g., assuming a person received hepatitis B vaccine
to comply with preschool or middle school entry require­
ments or participation in the U.S. military) might be con­
sidered, but such methods require further research before
they can be recommended as reliable alternatives.
• Determining immunity from previous infection through
serologic testing is an alternative to vaccination. How­
ever, using serologic testing to assess immunity from vac­
cination in persons with unknown or uncertain
vaccination status can be problematic (see Prevaccination
Serologic Testing for Susceptibility).
• Persons who reside in the United States but were vacci­
nated in other countries should be considered fully vacci­
nated if they have written documentation of >3 doses of
vaccine administered at recommended minimum
intervals, including the final dose at age >24 weeks. If
they were not vaccinated according to recommended mini­
mum intervals, they should be revaccinated (see Mini­
mum Dosing Intervals and Management of Persons Who
Were Vaccinated Incorrectly). Persons without written
documentation of full vaccination should receive doses
to complete the age-appropriate vaccine series.
Interrupted Vaccine Schedules
• When the hepatitis B vaccine schedule is interrupted, the
vaccine series does not need to be restarted.
• If the series is interrupted after the first dose, the second
dose should be administered as soon as possible, and the
second and third doses should be separated by an interval
of at least 8 weeks.
• If only the third dose has been delayed, it should be ad­
ministered as soon as possible.
27
Minimum Dosing Intervals
and Management of Persons
Who Were Vaccinated Incorrectly
• The third dose of vaccine must be administered at least
8 weeks after the second dose and should follow the first
dose by at least 16 weeks; the minimum interval between
the first and second doses is 4 weeks.
• Inadequate doses of hepatitis B vaccine (see Table 2) or
doses received after a shorter-than-recommended dosing
interval should be readministered, using the correct
dosage or schedule.
Accelerated Vaccine Schedules
• The Food and Drug Administration has not approved
accelerated schedules in which hepatitis B vaccine is
administered more than once in 1 month. If an accelerated
schedule (e.g., doses at 0, 7, and 14 days) is used, the patient
also should receive a booster dose at least 6 months after the
start of the series to promote long-term immunity.
Hemodialysis Patients and Other
Immunocompromised Persons
• Hepatitis B vaccination is recommended for pre–end-stage
renal disease patients before they become dialysis depen­
dent and for peritoneal and home dialysis patients
because they might require in-center hemodialysis.
• Higher hepatitis B vaccine doses are recommended for
adult dialysis patients and other immunocompromised
persons (see Table 2).
• Serologic testing of hemodialysis patients and other
immunocompromised persons is recommended 1–2
months after administration of the final dose of the pri­
mary vaccine series to determine the need for revaccina­
tion (see Postvaccination Testing for Serologic Response).
In addition, booster doses of vaccine might be needed
(see Booster Doses).
Prevaccination Serologic Testing
for Susceptibility
• Vaccination of persons who are immune to hepatitis B
virus (HBV) infection because of current or previous
infection or vaccination does not increase the risk for
adverse events. However, in adult populations that have
expected high rates of previous HBV infection,
prevaccination testing might reduce costs by avoiding
vaccination of persons who are already immune (Box).
Prevaccination testing is recommended for all foreign-born
28
MMWR
BOX. Method to determine cost-effectiveness of prevac­
cination screening for hepatitis B virus infection when the
first vaccine dose is administered at the time of blood draw
Prevaccination testing is cost effective when the cost
of serologic testing is less than or equal to the cost of
vaccinating persons who are already immune, as ex­
pressed by the formula
T <P1 x [P2 + P2(P3)] x v
where
T = cost of serologic testing (including cost of blood
draw);
P1 = prevalence of previous infection;
P2 = percentage of recipients of first dose who actually
receive a second dose;
P3 = percentage of recipients of doses 1 and 2 who receive
dose 3;
[P2 + P2 (P3)] = average number of doses for a person
starting the series; and
v = cost per dose of vaccine, including administrative
costs.
persons (including immigrants, refugees, asylum seekers,
and internationally adopted children) born in Africa, Asia,
the Pacific Islands, and other regions with high endemic­
ity of HBV infection (HBsAg prevalence of >8%) (see
Figure 4 and Box, Appendix C); for household, sex, and
needle-sharing contacts of HBsAg-positive persons; and
for HIV-infected persons (8). In addition, testing might
be cost effective in adult populations with a prevalence of
HBV infection of >20% (e.g., injection-drug users,
incarcerated persons, men who have sex with men; and
persons born in countries with intermediate levels of
endemic HBV infection [HBsAg prevalence of 2%–7%]
[see Figure 4 and Box 2]). In a study conducted in correc­
tional facilities, the cost of prevaccination testing was
equivalent to vaccination without testing at a threshold
prevalence of HBV infection of 25% (9).
• Prevaccination testing can be done with a single test (antiHBc) or with a panel of tests (e.g., HBsAg and anti-HBs).
The typical interpretation of HBV serologic markers has
been described (see Table 1).
• When a single test is used, testing for anti-HBc is pre­
ferred because it identifies all persons with previous HBV
infection, including persons with chronic HBV infection.
• If prevaccination testing for anti-HBs is used to identify
immunity after previous HBV infection, HBsAg testing
also must be performed to identify persons with chronic
HBV infection. However, for persons who were vacci­
December 8, 2006
nated previously or whose vaccination status is unknown,
interpretation of anti-HBs results can be problematic.
Postvaccination anti-HBs concentrations decline over
time, and vaccine responders remain protected even when
anti-HBs concentrations are no longer detectable; there­
fore, a negative anti-HBs result does not necessarily indi­
cate lack of immunity in vaccinated persons. In addition,
an anti-HBs-positive result can occur even for persons
who received >1 dose of vaccine but did not complete the
series. However, long-term protection has been
demonstrated only for persons who have completed a
licensed vaccination series and have ever had an anti-HBs
concentration of >10 mIU/mL; persons with an anti-HBs­
positive result but who did complete a vaccine schedule
might not have long-term protection from HBV infection.
• Serologic testing should not be a barrier to vaccination of
susceptible persons, especially in populations that are dif­
ficult to access. The first vaccine dose typically should be
administered immediately after collection of the blood
sample for serologic testing.
Postvaccination Testing for Serologic
Response
• Serologic testing for immunity is not necessary after
routine vaccination of adults.
• Testing after vaccination is recommended only for the
following persons whose subsequent clinical management
depends on knowledge of their immune status:
— Health-care workers and public safety workers at high
risk for continued percutaneous or mucosal exposure
to blood or body fluids (e.g., acupuncturists, dentists,
dental hygienists, emergency medical technicians, first
responders, laboratory technologists/technicians,
nurses, nurse practitioners, phlebotomists, physicians,
physician assistants, and students entering these pro­
fessions), to determine the need for revaccination and
to guide postexposure prophylaxis. Testing persons at
low risk for continued mucosal or percutaneous
exposure to blood or body fluids (e.g., public safety
workers and health-care workers without direct patient
contact) is not likely to be cost effective. Health-care
and public safety workers who have written documen­
tation of a complete vaccine series but who have never
had postvaccination testing do not need serologic test­
ing for anti-HBs unless they have a percutaneous or
mucosal exposure to blood or body fluids (10).
— Chronic hemodialysis patients, HIV-infected persons,
and other immunocompromised persons (e.g.,
hematopoietic stem-cell transplant recipients or per­
Vol. 55 / RR-16
•
•
•
•
Recommendations and Reports
sons receiving chemotherapy), to determine the need
for revaccination and the type of follow-up testing.
— Sex partners of HBsAg-positive persons, to determine
the need for revaccination and for other methods of
protection against HBV infection.
Testing should be performed 1–2 months after adminis­
tration of the last dose of the vaccine series using a method
that allows determination of a protective concentration
of anti-HBs (>10 mIU/mL).
Persons found to have anti-HBs concentrations of >10
mIU/mL after the primary vaccine series are considered
to be immune.
— Immunocompetent persons have long-term protection
and do not need further periodic testing to assess antiHBs levels.
— Immunocompromised persons might need annual test­
ing to assess anti-HBs concentrations (see Booster
Doses).
Persons found to have anti-HBs concentrations of <10
mIU/mL after the primary vaccine series should be
revaccinated. Administration of 3 doses on an appropri­
ate schedule (see Box 5), followed by anti-HBs testing
1–2 months after the third dose, usually is more practical
than serologic testing after 1 or more doses of vaccine.
Persons who do not have a protective concentration of
anti-HBs after revaccination should be tested for HBsAg.
— If the HBsAg test result is positive, the person should
receive appropriate management, and any household,
sex, or needle-sharing contacts should be identified and
vaccinated (see Appendix C).
— Persons who test negative for HBsAg should be con­
sidered susceptible to HBV infection and should be
counseled about precautions to prevent HBV infec­
tion and the need to obtain HBIG postexposure pro­
phylaxis for any known or likely parenteral exposure
to HBsAg-positive blood (10).
Booster Doses
• Booster doses are not recommended for persons with
normal immune status who were vaccinated as infants,
children, adolescents, or adults. Serologic testing is not
recommended to assess antibody concentrations in any
29
age group, except in certain circumstances (see Postvacci­
nation Testing for Serologic Response).
• For hemodialysis patients, the need for booster doses
should be assessed by annual anti-HBs testing. A booster
dose should be administered when anti-HBs levels
decline to <10 mIU/mL.
• For other immunocompromised persons (e.g., HIVinfected persons, hematopoietic stem-cell transplant
recipients, and persons receiving chemotherapy), the need
for booster doses has not been determined. When antiHBs levels decline to <10 mIU/mL, annual anti-HBs test­
ing and booster doses should be considered for persons
with an ongoing risk for exposure.
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intradermal hepatitis B immunization and response to a booster dose.
Vaccine 1992;10:33–8.
6. Coberly JS, Townsend T, Repke J, Fields H, Margolis H, Halsey NA.
Suboptimal response following intradermal hepatitis B vaccine in
infants. Vaccine 1994;12:984–7.
7. CDC. General recommendations on immunization 2006: recommen­
dations of the Advisory Committee on Immunization Practices (ACIP).
MMWR. In press.
8. CDC. Treating opportunistic infections among HIV-infected adults
and adolescents: recommendations from CDC, the National Institutes
of Health, and the HIV Medicine Association/Infectious Diseases
Society of America. MMWR 2004;53(No. RR-15).
9. CDC. Hepatitis B vaccination of inmates in correctional facilities—
Texas, 2000–2002. MMWR 2004;53:681–3.
10. CDC. Updated U.S. Public Health Service guidelines for the
management of occupational exposures to HBV, HCV, and HIV
and recommendations for postexposure prophylaxis. MMWR 2001;
50(No. RR-11).
30
MMWR
December 8, 2006
Appendix B
Postexposure Prophylaxis to Prevent Hepatitis B Virus Infection
This appendix provides guidelines for management of
persons with nonoccupational exposure to hepatitis B virus
(HBV) through a discrete, identifiable exposure to blood or
body fluids (Table). Guidelines for postexposure prophylaxis
of occupational exposures have been published separately (1)
and are intended for use in settings in which postvaccination
testing is recommended for certain employees (see Appendix
A, Postvaccination Testing for Serologic Response) and in
which programs are available to implement testing and fol­
low-up algorithms. Recommendations for management of
infants born to hepatitis B surface antigen (HBsAg)–positive
mothers also have been published separately (2).
HBsAg-Positive Exposure Source
• Persons who have written documentation of a complete
hepatitis B vaccine series and who did not receive postvac­
cination testing should receive a single vaccine booster dose.
• Persons who are in the process of being vaccinated but
who have not completed the vaccine series should receive
the appropriate dose of hepatitis B immune globulin
(HBIG) and should complete the vaccine series.
• Unvaccinated persons should receive both HBIG and
hepatitis B vaccine as soon as possible after exposure (pref­
erably within 24 hours). Hepatitis B vaccine may be
administered simultaneously with HBIG in a separate
injection site. The hepatitis B vaccine series should be
completed in accordance with the age-appropriate vac­
cine dose and schedule (see Table 2 and Box 5).
Exposure Source with Unknown HBsAg
Status
• Persons with written documentation of a complete
hepatitis B vaccine series require no further treatment.
• Persons who are not fully vaccinated should complete the
vaccine series.
• Unvaccinated persons should receive the hepatitis B vac­
cine series with the first dose administered as soon as pos­
sible after exposure, preferably within 24 hours. The
TABLE. Guidelines for postexposure prophylaxis* of persons with nonoccupational exposures† to blood or body fluids that
contain blood, by exposure type and vaccination status
Treatment
Unvaccinated person§
Previously vaccinated person¶
Percutaneous (e.g., bite or needlestick) or mucosal
exposure to HBsAg-positive blood or body fluids
Administer hepatitis B vaccine series and
hepatitis B immune globulin (HBIG)
Administer hepatitis B vaccine
booster dose
Sex or needle-sharing contact of an HBsAg-positive person
Administer hepatitis B vaccine series and
HBIG
Administer hepatitis B vaccine
booster dose
Victim of sexual assault/abuse by a perpetrator who is
HBsAg positive
Administer hepatitis B vaccine series and
HBIG
Administer hepatitis B vaccine
booster dose
Source with unknown HBsAg status
Victim of sexual assault/abuse by a perpetrator with
unknown HBsAg status
Administer hepatitis B vaccine series
No treatment
Percutaneous (e.g., bite or needlestick) or mucosal
exposure to potentially infectious blood or body fluids
from a source with unknown HBsAg status
Administer hepatitis B vaccine series
No treatment
Sex or needle-sharing contact of person with unknown
HBsAg status
Administer hepatitis B vaccine series
No treatment
Exposure
HBsAg**-positive source
* When indicated, immunoprophylaxis should be initiated as soon as possible, preferably within 24 hours. Studies are limited on the maximum interval
after exposure during which postexposure prophylaxis is effective, but the interval is unlikely to exceed 7 days for percutaneous exposures or 14 days
for sexual exposures. The hepatitis B vaccine series should be completed.
† These guidelines apply to nonoccupational exposures. Guidelines for management of occupational exposures have been published separately (1) and
also can be used for management of nonoccupational exposures, if feasible.
§ A person who is in the process of being vaccinated but who has not completed the vaccine series should complete the series and receive treatment as
indicated.
¶ A person who has written documentation of a complete hepatitis B vaccine series and who did not receive postvaccination testing.
** Hepatitis B surface antigen.
Vol. 55 / RR-16
Recommendations and Reports
vaccine series should be completed in accordance with
the age-appropriate dose and schedule (see Table 2 and
Box 5).
References
1. CDC. Updated U.S. Public Health Service guidelines for the
management of occupational exposures to HBV, HCV, and HIV
and recommendations for postexposure prophylaxis. MMWR 2001;
50(No. RR-11).
31
2. CDC. A comprehensive immunization strategy to eliminate transmis­
sion of hepatitis B virus infection in the United States: recommenda­
tions of the Advisory Committee on Immunization Practices (ACIP).
Part 1: immunization of infants, children, and adolescents. MMWR
2005;54(No. RR-16).
32
MMWR
December 8, 2006
Appendix C
Identification and Management of Hepatitis B
Surface Antigen (HBsAg)–Positive Persons
Persons with chronic hepatitis B virus (HBV) infection are
at high risk for chronic liver disease and are a major reservoir
of HBV infection. Foreign-born populations from Africa, Asia,
and the Pacific Islands have high rates of chronic HBV infec­
tion (i.e., HBsAg prevalence of >8%). During delivery of rec­
ommended hepatitis B vaccination services (e.g., HBsAg
screening of pregnant women and serologic testing to assess
susceptibility), vaccination providers will identify persons who
are HBsAg positive. These persons require counseling and
medical management for chronic HBV infection to reduce
their risk for chronic liver disease. Their susceptible house­
hold, sex, and needle-sharing contacts also should be vacci­
nated against hepatitis B.
Extending screening, referral, and contact vaccination ser­
vices to persons identified as HBsAg positive can help prevent
serious sequelae in persons with chronic infection and enhance
vaccination strategies to eliminate HBV transmission. This
appendix provides guidance for vaccination providers concern­
ing identification and management of persons with chronic
HBV infection. These guidelines are not intended to repre­
sent a comprehensive prevention program for persons with
chronic infection.
Identification of Persons Who Are
Potentially HBsAg Positive
• All foreign-born persons (including immigrants, refugees,
asylum seekers, and internationally adopted children) from
Africa, Asia, the Pacific Islands, and other regions with
high endemicity of HBV infection (Box) should be tested
for HBsAg, regardless of vaccination status.
— For all persons born in countries in which HBV is
highly endemic who are applying for permanent U.S.
residence, HBsAg screening and appropriate followup on the basis of HBsAg test results should be
included as part of the required overseas premigration
and domestic adjustment-of-visa status medical exami­
nation process; information about this process is avail­
able at http://www.cdc.gov/ncidod/dq/health.htm.
HBsAg-positive persons should be considered eligible
for migration and adjustment-of-visa status and coun­
seled and recommended for follow-up medical evalua­
tion and management in U.S. resettlement communities.
— In all settings that provide health care, providers should
identify persons born in countries in which HBV infec-
BOX. Geographic regions* with high † hepatitis B virus
endemicity
Africa: all countries except Algeria, Djibouti, Egypt,
Libya, Morocco, and Tunisia
Southeast Asia: all countries except Malaysia
East Asia: China, Hong Kong, Mongolia, North Korea,
South Korea, and Taiwan
Australia and South Pacific: all countries except
Australia, Guam, and New Zealand
Middle East: Jordan and Saudi Arabia
Eastern Europe and Northern Asia: Albania, Armenia,
Azerbaijan, Bulgaria, Croatia, Georgia, Kazakhstan,
Kyrgyzstan, Moldova, Tajikistan, Turkmenistan, and
Uzbekistan
Western Europe: Malta and indigenous populations in
Greenland
North America: Alaska Natives and indigenous
populations in Northern Canada
South America: Amazonian areas of Bolivia, Brazil,
Columbia, Peru, and Venezuela
Caribbean: Turks and Caicos
* A complete list of countries in each region is available at http://www.cdc.
gov/travel/destinat.htm.
† Hepatitis B surface antigen prevalence of >8%.
tion is highly endemic and provide HBsAg testing and
follow-up. Retesting of persons who were tested for
HBsAg in other countries should be considered.
• Other persons who should be tested for HBsAg as part of
vaccination services include
— all pregnant women (1);
— persons who receive prevaccination testing for suscep­
tibility and who test positive for anti-HBc (see
Appendix A, Prevaccination Serologic Testing for
Susceptibility);
— hemodialysis patients; and
— nonresponders to vaccination (see Appendix A, Post­
vaccination Testing for Serologic Response).
Management of Persons Identified
as HBsAg Positive
• All HBsAg-positive laboratory results should be reported
to the state or local health department, in accordance with
Vol. 55 / RR-16
•
•
•
•
•
Recommendations and Reports
state requirements for reporting of chronic HBV infec­
tion; information about state requirements is available at
http://www.cste.org/NNDSSSurvey/2004NNDSS/
nndssstatechrreporcond2005.asp.
HBsAg-positive persons should be referred for evaluation to
a physician experienced in the management of chronic liver
disease; a directory of liver specialists is available at
http://www.hepb.org/resources/other_links_physician.htm.
Certain patients with chronic HBV infection will benefit
from early intervention with antiviral treatment, manage­
ment of factors that can contribute to disease progres­
sion, or screening to detect hepatocellular carcinoma at an
early stage.
Household, sex, and needle-sharing contacts of HBsAg­
positive persons should be identified. Unvaccinated sex
partners and household and needle-sharing contacts
should be tested for susceptibility to HBV infection (see
Appendix A, Prevaccination Serologic Testing for Suscep­
tibility) and should receive the first dose of hepatitis B
vaccine immediately after collection of blood for sero­
logic testing. Susceptible persons should complete the
vaccine series using an age-appropriate vaccine dose and
schedule (see Table 2 and Box 5). Persons who are not
fully vaccinated should complete the vaccine series.
Sex partners of HBsAg-positive persons should be coun­
seled to use methods (e.g., condoms) to protect them­
selves from sexual exposure to infectious body fluids (e.g.,
semen or vaginal secretions) unless they have been dem­
onstrated to be immune after vaccination (i.e., antibody
to HBsAg concentrations of >10 mIU/mL) or previously
infected (anti-HBc positive). Partners should be made
aware that use of condoms and other prevention meth­
ods might reduce their risks for human immunodeficiency
virus (HIV) and other sexually transmitted diseases
(STDs).
To prevent or reduce the risk for transmission to others,
HBsAg-positive persons should be advised concerning the
risks for
— perinatal transmission to infants born to HBsAg­
positive women and the need for such infants to
receive hepatitis B vaccine beginning at birth (1) and
— transmission to household, sex, and needle-sharing
contacts and the need for such contacts to receive hepa­
titis B vaccine.
HBsAg-positive persons should also be advised to
— notify their sex partners about their status;
— use methods (e.g., condoms) to protect nonimmune
sex partners from acquiring HBV infection from sexual
activity until the sex partners can be vaccinated and
33
their immunity documented (persons should be made
aware that use of condoms and other prevention meth­
ods might reduce their risks for HIV and other STDs);
— cover cuts and skin lesions to prevent spread through
infectious secretions or blood;
— refrain from donating blood, plasma, tissue, or semen
(organs may be donated to HBV-immune or chroni­
cally infected persons needing a transplant; decisions
about organ donation should be made on an individual
basis); and
— refrain from sharing household articles (e.g., tooth­
brushes, razors, or personal injection equipment) that
could become contaminated with blood.
• To protect the liver from further harm, HBsAg-positive
persons should be advised to
— avoid or limit alcohol consumption because of the
effects of alcohol on the liver;
— refrain from taking any new medicines, including over­
the-counter and herbal medicines, without consulting
with their health-care provider; and
— obtain vaccination against hepatitis A if chronic liver
disease is present (2).
• When seeking medical or dental care, HBsAg-positive
persons should be advised to inform those responsible for
their care of their HBsAg status so that they can be evalu­
ated and their care managed appropriately.
• Other counseling messages include the following:
— HBV is not spread by breastfeeding, kissing, hugging,
coughing, ingesting food or water, sharing eating uten­
sils or drinking glasses, or casual contact.
— Persons should not be excluded from work, school,
play, child care, or other settings on the basis of their
HBsAg status, unless they are prone to biting (3).
— Involvement with a support group might help patients cope
with chronic HBV infection. Information about support
groups is available at http://www.hepprograms.org/support/
hepb.asp and http://www.hepb.org/patients/support_
groups.htm.
References
1. CDC. A comprehensive immunization strategy to eliminate transmis­
sion of hepatitis B virus infection in the United States: recommenda­
tions of the Advisory Committee on Immunization Practices (ACIP).
Part 1: immunization of infants, children, and adolescents. MMWR
2005;54(No. RR-16).
2. CDC. Prevention of hepatitis A through active or passive immuniza­
tion: recommendations of the Advisory Committee on Immunization
Practices (ACIP). MMWR 2006;55(No. RR-7).
3. Shapiro CN, McCaig LF, Gensheimer KF, et al. Hepatitis B virus trans­
mission between children in day care. Pediatr Infect Dis J 1989;8:870–5.
Morbidity and Mortality Weekly Report
Recommendations and Reports
December 8, 2006 / Vol. 55 / No. RR-16
Continuing Education Activity Sponsored by CDC
A Comprehensive Immunization Strategy to Eliminate Transmission of Hepatitis B Virus Infection
in the United States: Recommendations of the Advisory Committee on Immunization Practices (ACIP)
Part II: Immunization of Adults
EXPIRATION — December 8, 2009
You must complete and return the response form electronically or by mail by
December 8, 2009, to receive continuing education credit. If you answer all
of the questions, you will receive an award letter for 3.0 hours Continuing
Medical Education (CME) credit; 0.25 Continuing Education Units (CEUs); or
3.0 contact hours Continuing Nursing Education (CNE) credit. If you return the
form electronically, you will receive educational credit immediately. If you mail
the form, you will receive educational credit in approximately 30 days. No fees are
charged for participating in this continuing education activity.
INSTRUCTIONS
By Internet
1. Read this MMWR (Vol. 55, RR-16), which contains the correct answers to
the questions beginning on the next page.
2. Go to the MMWR Continuing Education Internet site at http://www.cdc.
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3. Select which exam you want to take and select whether you want to register
for CME, CEU, or CNE credit.
4. Fill out and submit the registration form.
5. Select exam questions. To receive continuing education credit, you must
answer all of the questions. Questions with more than one correct answer
will instruct you to “Indicate all that apply.”
6. Submit your answers no later than December 8, 2009.
7. Immediately print your Certificate of Completion for your records.
By Mail or Fax
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the questions beginning on the next page.
2. Complete all registration information on the response form, including your
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3. Indicate whether you are registering for CME, CEU, or CNE credit.
4. Select your answers to the questions, and mark the corresponding letters on
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answer all of the questions. Questions with more than one correct answer
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5. Sign and date the response form or a photocopy of the form and send no
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ACCREDITATION
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depar
tment of health and human ser
vices
department
services
vices
Centers for Disease Control and Prevention
Prevention
CE-2
MMWR
December 8, 2006
Goal and Objectives
This report updates the immunization strategy to eliminate hepatitis B virus (HBV) transmission in the United States. The report includes new recommendations
regarding which adults should receive hepatitis B vaccine and provides implementation strategies to ensure that those adults are vaccinated. The goal of the report
is to provide strategies for health-care professionals to increase hepatitis B vaccination coverage among adults at risk for HBV infection. Strategies are directed toward
settings in which a high proportion of persons have risks for HBV infection and primary care and specialty medical settings in which persons at risk for HBV infection
receive care. Upon completion of this educational activity, the reader should be able to 1) identify adults who are recommended to receive hepatitis B vaccination,
2) identify settings in which a high proportion of persons are likely to be at risk for HBV infection, 3) identify components of a successful adult hepatitis B vaccination
program, 4) identify strategies to increase vaccination coverage among adults at risk for HBV infection, 5) describe practices that should be implemented in settings
in which adults receive hepatitis B vaccine, and 6) describe adult vaccination schedules.
To receive continuing education credit, please answer all of the following questions.
1. In which settings is universal hepatitis B vaccination recommended
because of the high proportion of adults with behavioral risk factors
for HBV infection?
A. Sexually transmitted disease and human immunodeficiency virus
(STD/HIV) testing and treatment facilities.
B. Drug-abuse treatment and prevention settings.
C. Health-care settings targeting services to men who have sex with men
(MSM).
D. Correctional facilities.
E. Hospitals.
2. The Advisory Committee on Immunization Practices (ACIP)
recommends standing orders to identify adults recommended for
hepatitis B vaccination and administer vaccination as part of routine
services in primary care and specialty medical settings.
A. True.
B. False.
3. Which of the following practices should be implemented in primary
care and specialty medical settings to ensure vaccination of adults at
risk for HBV infection? (Indicate all that apply.)
A. Provide information to all adults regarding the benefits of hepatitis B
vaccination, including the risk factors for HBV infection and persons
for whom vaccination is recommended.
B. Help adults assess their need for vaccination by obtaining a history that
emphasizes risks for sexual transmission and percutaneous or mucosal
exposure to blood.
C. Provide hepatitis B vaccine to persons who report risk factors for HBV
infection.
D. Request that adults acknowledge a specific factor for HBV infection
before offering hepatitis B vaccine.
4. Which of the following are components of a successful adult hepatitis
B vaccination program? (Indicate all that apply.)
A. Protocols and standing orders.
B. Protected patient confidentiality.
C. Trained and knowledgeable staff.
D. Funding for vaccine.
E. Billing and reimbursement mechanisms.
5. Which of the following persons are recommended to receive hepatitis
B vaccine because they have a risk factor for HBV infection? (Indicate
all that apply.)
A. Sexually active persons who are not in a long-term, mutually
monogamous relationship.
B. Injection-drug users.
C. MSM.
D. Persons who live in a household with a person who is hepatitis B surface
antigen (HBsAg)–positive.
E. Persons seeking treatment for an STD.
F. Pregnant women.
6. Which of the following statements regarding hepatitis B vaccination
are true? (Indicate all that apply.)
A. Hepatitis B vaccine is available as a single-antigen formulation only.
B. Primary vaccination against hepatitis B consists of 3 doses
administered at 0, 1, and 6 months.
C. Increasing the interval between the first 2 doses has little effect on
immunogenicity or final antibody concentration.
D. Differences in immunogenicity have been observed when hepatitis B
vaccines produced by different manufacturers are used to complete the
vaccine series.
E. Routine vaccination of adults should be followed by postvaccination
testing to determine serologic response.
7. Which of the following statements regarding immune memory for
hepatitis B are true? (Indicate all that apply.)
A. Antibody to HBsAg (anti-HBs) is the only easily measurable correlate
of vaccine-induced protection.
B. After primary vaccination with hepatitis B vaccine, anti-HBs
concentrations decline rapidly within the first year.
C. When anti-HBs concentrations decline to <10 mIU/mL, all
vaccinated persons should receive a booster dose of hepatitis B vaccine.
D. A booster dose of hepatitis B vaccine is recommended 10 years after the
3rd dose of vaccine was received.
8. Which of the following statements regarding hepatitis B immune
globulin (HBIG) are true? (Indicate all that apply.)
A. HBIG provides temporary protection when administered in standard
doses.
B. HBIG typically is used instead of hepatitis B vaccine for postexposure
immunoprophylaxis to prevent HBV infection.
C. No evidence exists that HBV, hepatitis C virus, or HIV have ever been
transmitted by HBIG in the United States.
D. HBIG administered alone is the primary means of protection after an
HBV exposure for nonresponders to hepatitis B vaccination.
9. Postvaccination testing is recommended for which of the following
populations? (Indicate all that apply.)
A. Certain health-care and public safety workers.
B. Chronic hemodialysis patients.
C. HIV-infected persons.
D. HCV-infected persons.
E. Sex partners of HBsAg-positive persons.
10. Which best describes your professional activities?
A. Physician.
B. Nurse.
C. Health educator.
D. Office staff.
E. Other.
11. I plan to use these recommendations as the basis for… (Indicate all
that apply.)
A. health education materials.
B. insurance reimbursement policies.
C. local practice guidelines.
D. public policy.
E. other.
Vol. 55 / No. RR-16
Recommendations and Reports
CE-3
16. After reading this report, I am confident I can identify strategies to
increase vaccination coverage among adults at risk for HBV infection.
A. Strongly agree.
B. Agree.
C. Undecided.
D. Disagree.
E. Strongly disagree.
12. Overall, the length of the journal report was…
A. much too long.
B. a little too long.
C. just right.
D. a little too short.
E. much too short.
13. After reading this report, I am confident I can identify adults who are
recommended to receive hepatitis B vaccination.
A. Strongly agree.
B. Agree.
C. Undecided.
D. Disagree.
E. Strongly disagree.
17. After reading this report, I am confident I can describe practices that
should be implemented in settings in which adults receive hepatitis B
vaccine.
A. Strongly agree.
B. Agree.
C. Undecided.
D. Disagree.
E. Strongly disagree.
14. After reading this report, I am confident I can identify settings in
which a high proportion of persons are likely to be at risk for HBV
infection.
A. Strongly agree.
B. Agree.
C. Undecided.
D. Disagree.
E. Strongly disagree.
18. After reading this report, I am confident I can describe adult
vaccination schedules.
A. Strongly agree.
B. Agree.
C. Undecided.
D. Disagree.
E. Strongly disagree.
15. After reading this report, I am confident I can identify components of
a successful adult hepatitis B vaccination program.
A. Strongly agree.
B. Agree.
C. Undecided.
D. Disagree.
E. Strongly disagree.
19. The learning outcomes (objectives) were relevant to the goals of this
report.
A. Strongly agree.
B. Agree.
C. Undecided.
D. Disagree.
E. Strongly disagree.
(Continued on pg CE-4)
Date I Completed Exam
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E-Mail Address
Fill in the appropriate blocks to indicate your answers. Remember, you must answer all
of the questions to receive continuing education credit!
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or
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CME Credit
CME for
nonphysicians
Credit
CEU Credit
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To receive continuing education credit, you must
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2. indicate your choice of CME, CME for nonphysicians, CEU, or CNE credit;
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A Comprehensive Immunization Strategy to Eliminate Transmission of Hepatitis B
Virus Infection in the United States: Recommendations of the Advisory Committee
on Immunization Practices (ACIP) Part II: Immunization of Adults
MMWR Response Form for Continuing Education Credit
December 8, 2006/Vol. 55/No. RR-16
Detach or photocopy.
CE-4
MMWR
December 8, 2006
20. The instructional strategies used in this report (text, tables, figures,
boxes, and appendices) helped me learn the material.
A. Strongly agree.
B. Agree.
C. Undecided.
D. Disagree.
E. Strongly disagree.
25. The availability of continuing education credit influenced my
decision to read this report.
A. Strongly agree.
B. Agree.
C. Undecided.
D. Disagree.
E. Strongly disagree.
21. The content was appropriate given the stated objectives of the report.
A. Strongly agree.
B. Agree.
C. Undecided.
D. Disagree.
E. Strongly disagree.
26. The MMWR format was conducive to learning this content.
A. Strongly agree.
B. Agree.
C. Undecided.
D. Disagree.
E. Strongly disagree.
23. Overall, the quality of the journal report was excellent.
A. Strongly agree.
B. Agree.
C. Undecided.
D. Disagree.
E. Strongly disagree.
24. These recommendations will improve the quality of my practice.
A. Strongly agree.
B. Agree.
C. Undecided.
D. Disagree.
E. Strongly disagree.
27. Do you feel this course was commercially biased? (Indicate yes or no;
if yes, please explain in the space provided.)
A. Yes.
B. No.
28. How did you learn about the continuing education activity?
A. Internet.
B. Advertisement (e.g., fact sheet, MMWR cover, newsletter, or journal).
C. Coworker/supervisor.
D. Conference presentation.
E. MMWR subscription.
F. Other.
Correct answers for questions 1–9.
1. A, B, C, and D. 2. A. 3. A, B, and C. 4. A, B, C, D, and E. 5. A, B, C, D,
and E. 6. B and C. 7. A and B. 8. A, C, and D. 9. A, B, C, and E.
22. The content expert(s) demonstrated expertise in the subject matter.
A. Strongly agree.
B. Agree.
C. Undecided.
D. Disagree.
E. Strongly disagree.
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